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High-resolution computed tomography image in a case of severe idiopathic pulmonary fibrosis. Diffuse honeycombing and traction bronchiectasis are present.
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Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to...
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Citations
... In addition, preliminary data suggested the efficacy of both antifibrotic agents in severe IPF with lung function impairment (FVC < 50%). (25). In the present study, most of IPF patients were treated with doses of both nintedanib (200 mg/day) and pirfenidone (600-1200 mg/day) due to tolerability issues. ...
Background and aim
Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown.
Methods
We retrospectively investigated favorable factors of survival in consecutive 55 IPF patients with chronic respiratory failure who were introduced LTOT.
Results
The 6-, 12-, 18-, and 24-month survival rates in IPF patients after introduction of LTOT were 70.9%, 49.0%, 45.2%, and 32.3%, respectively. Univariate analysis demonstrated that low Glasgow Prognostic Score (GPS) (hazard ratio [HR] 0.482, p=0.043) and treatment with antifibrotic agents (HR 0.401, p=0.013) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 0.449, p=0.032). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0106).
Conclusion
In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.
... In general, the progression of IPF is not linear [4][5][6]; some patients may experience rapid deterioration and progression to death, whereas others can experience periods of relative stability followed by periods of acute respiratory decline [1,7]. There is no standardized definition for the staging of IPF [3,4]; however, IPF staging has traditionally been defined by terms such as ''mild,'' ''moderate,'' and ''severe'' or ''early'' and ''advanced,'' and has typically been based on pulmonary function test results [4,[8][9][10]. Previous studies have generally classified patients with IPF as having mild-to-moderate lung impairment based on a percent predicted forced vital capacity (%FVC) of C 50% to 55% and a percent predicted carbon monoxide diffusing capacity (%DLco) of C 30% to 40%, while those with severe or advanced IPF have been classified as having %FVC and %DLco values lower than these thresholds [4,[11][12][13][14]. ...
Introduction:
In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis (IPF). This analysis compared the efficacy and safety of pirfenidone in advanced IPF versus non-advanced IPF.
Methods:
Data were included from the following studies of pirfenidone: ASCEND (NCT01366209); CAPACITY (004 [NCT00287716] and 006 [NCT00287729]); RECAP (NCT00662038; advanced IPF defined as percent predicted forced vital capacity [%FVC] < 50% and/or percent predicted carbon monoxide diffusing capacity [%DLco] < 35% at baseline); PASSPORT (NCT02699879; advanced IPF defined as baseline %FVC < 50%); and SP-IPF (NCT02951429; patients with advanced IPF [defined as %DLco ≤ 40% at screening] at risk of group 3 pulmonary hypertension).
Results:
In the pooled ASCEND/CAPACITY studies, the annual mean rate of FVC decline from baseline to Week 52 was significantly lower for pirfenidone versus placebo in advanced (p = 0.0035) and non-advanced IPF (p = 0.0001). Rate of all-cause mortality over 52 weeks was numerically lower for pirfenidone versus placebo in advanced and non-advanced IPF. In RECAP, the mean annual rate of FVC decline from baseline to Week 180 of pirfenidone treatment was similar in patients with advanced (- 141.5 mL) and non-advanced IPF (- 153.5 mL). In SP-IPF, the mean annual rate of FVC decline and rate of all-cause mortality from baseline to Week 52 in patients treated with placebo + pirfenidone were - 93.0 mL and 20.2%, respectively. No new safety signals were identified, and the safety profile of pirfenidone in patients with advanced IPF was generally consistent with that of non-advanced IPF.
Conclusions:
These results highlight the benefit of pirfenidone treatment in patients with advanced and non-advanced IPF. As such, the indication for pirfenidone in the EU has now been updated to include the treatment of adult patients with advanced IPF.
Trial registrations:
ASCEND (NCT01366209), CAPACITY 004 (NCT00287716), CAPACITY 006 (NCT00287729), RECAP (NCT00662038), PASSPORT (NCT02699879), and SP-IPF (NCT02951429).
... If presenting late, patients may have features of pulmonary hypertension, corpulmonale, and right heart failure. [1,4,13,14] The diagnosis of IPF requires the exclusion of other known causes of ILD and a typical usual interstitial pneumonia (UIP) pattern on high resolution computed tomography (HRCT) in patients not subjected to lung biopsy. [15] Pulmonary function tests in patients with IPF usually show a restrictive pattern, with a reduced forced vital capacity (FVC) and normal to high forced expiratory volume in 1 s (FEV1) to FVC ratio, low residual volume (RV) and total lung capacity (TLC), and a reduced transfer factor of the lung for carbon monoxide (TLCO), which typically declines with disease progression. ...
... These findings are similar to those found in existing articles from both developing and developed countries. [13,14,[35][36][37] While baseline FVC and FEV1 in this cohort were similar to those found by Collard et al, [37] RV and TLCO were markedly lower in our patients. This adds further evidence to the presence of advanced disease on presentation. ...
Objectives
Idiopathic pulmonary fibrosis (IPF) is a specific form of age-related fibroproliferative interstitial pneumonia that is chronic, progressive, and carries a poor prognosis, with median survival of just 2.5–3.5 years from diagnosis. The exact etiology is unknown, but smoking is known to be risk factor. Symptoms and signs include progressive dyspnoea, cough, inspiratory “Velcro” crackles, and clubbing. At present, treatment options are limited; but include pulmonary rehabilitation, long-term domiciliary oxygen therapy, and the conditionally recommended pharmacological therapies pirfenidone and nintedanib. This study sought to describe the cohort of patients that attended the respiratory outpatient services at a tertiary-level hospital in South Africa during the period 2007– 2016. To the best of the authors’ knowledge, this is the first such descriptive study performed in Africa.
Materials and Methods
This was a retrospective, descriptive, and record review, that included patients ≥18 years of age who fulfilled 2011 ATS/ERS/JRS/ALAT diagnostic criteria for IPF.
Results
Data from 74 patients were used for analysis in this study, of which 60.8% were female. The mean age standard deviation was 64.4 (10.9) years and the majority (79.7%) were Black. Over half of the patients (40/74, 54.1%) were current or previous smokers, although there was no correlation between smoking history and age or baseline pulmonary function testing. All patients reported dyspnea, which was modified Medical Reseach Council (mMRC) Grade 3 or 4 in 80% of patients. High resolution computed tomography chest was reported as radiological usual interstitial pneumonia (UIP) in 72 patients (97.3%) and three patients underwent lung biopsy, all of which showed a UIP pattern. Fifty-eight patients (78.4%) had spirometry results available, with median forced vital capacity 67.3% of predicted; this was significantly higher in females. Median transfer factor of the lung for carbon monoxide was 39% predicted. Twenty-five patients (33.8%) received corticosteroids, of whom five (6.8%) received the prednisone-azathioprine-N-acetylcysteine regime. Three patients (4.1%) received nintedanib; two of whom showed slowing of decline in lung function, although no significant symptomatic improvement was reported. Mean duration of follow-up was 13.3 months, although females had significantly longer duration of follow-up than males.
Conclusion
Despite a fairly small sample size and retrospective nature, this study contributes to the body of literature on IPF and highlights the need for additional studies in developing countries, particularly in Africa.
... These drugs help to prevent further scarring and slow the progression of the disease, but do not cure IPF. In addition, there are insufficient data on proven effective treatments for severe IPF, although it may also be because patients with severe IPF usually not participate in randomized, prospective, multicenter, international trials [86]. It is necessary to find novel effective treatment strategy for IPF. ...
Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, and it has a worse prognosis than non-small cell lung cancer. The pathomechanism of IPF is not fully understood, but it has been suggested that repeated microinjuries of epithelial cells induce a wound healing response, during which fibroblasts differentiate into myofibroblasts. These activated myofibroblasts express α smooth muscle actin and release extracellular matrix to promote matrix deposition and tissue remodeling. Under physiological conditions, the remodeling process stops once wound healing is complete. However, in the lungs of IPF patients, myofibroblasts re-main active and deposit excess extracellular matrix. This leads to the destruction of alveolar tissue, the loss of lung elastic recoil, and a rapid decrease in lung function. Some evidence has indicated that proteasomal inhibition combats fibrosis by inhibiting the expressions of extracellular matrix proteins and metalloproteinases. However, the mechanisms by which proteasome inhibitors may protect against fibrosis are not known. This review summarizes the current research on proteasome inhibitors for pulmonary fibrosis, and provides a reference for whether proteasome inhibitors have the potential to become new drugs for the treatment of pulmonary fibrosis.
... In addition, preliminary data suggested the e cacy of both anti brotic agents in severe IPF with lung function impairment (FVC < 50%). (23). In the present study, most of IPF patients were treated with doses of both nintedanib (200mg/day) and pirfenidone (600-1200mg/day) due to tolerability issues. ...
Background:
Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown.
Methods:
We retrospectively investigated favorable factors of survival in 52 IPF patients who were introduced LTOT.
Results:
The 6-, 12-, and 24-month survival rates in IPF patients after introduction of LTOT were 72.8%, 48.3%, and 28.9%, respectively. Univariate analysis demonstrated that gender female (hazard ratio [HR] 7.394, p=0.049) and treatment with antifibrotic agents (HR 2.285, p=0.022) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 2.121, p=0.037). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0165).
Conclusion:
In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Continuous treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.
... While attempts have been made to quantify HRQoL for persons living with IPF in Australia, these have either been by using non-preference-based measures for HRQoL or HSUVs generated from RCTs [31][32][33][34][35][36]. A limitation of the use of non-preference based measures is that their use for economic evaluations is limited if a validated indirect method/mapping algorithm has not been established [37] and often with IPF RCTs, persons with severe disease comprise a small proportion or are not included [38] which may bias the results. When we consider the mean HSUV for our cohort, (0.65, 95% CI 0.61-0.70) the results compare reasonably well to the current literature, more specifically, German cohorts, 0.66-0.67 ...
PurposeIdiopathic pulmonary fibrosis (IPF) is a progressive and universally fatal lung disease, characterised by increasing fibrosis of the lung parenchyma. In this study, we aimed to quantify the health state utility values (HSUVs) for Australians with IPF and to identify the factors affecting these HSUVs.
Methods
Participants of the Australian IPF Registry (AIPFR), with data on EuroQoL five dimension—five level (EQ-5D-5L) profiles were included. Pulmonary function tests (PFTs) were used to assess disease severity using three IPF -based classification systems. Stepwise multivariable linear regression models assessed the relationship between HSUVs and important demographic and clinical parameters.Query
ResultsA total of 155 participants provided data for the analysis of HSUVs. For our base case, HSUVs ranged from − 0.57 to 1.00. Mean HSUVs for all participants was 0.65 (95% CI 0.61–0.70). In general, HSUVs decreased with increasing disease severity under all disease severity classification systems. Multivariable linear regression demonstrated a negative association between HSUVs, disease severity and having more than 2 comorbidities.
Conclusions
Our study has shown that EQ-5D-5L has exhibited discriminatory sensitivity for the study population. We have demonstrated that disease severity and having more than two comorbidities was associated with lower HSUVs in Australians with IPF. Our findings support early diagnosis and appropriate evidence-based treatment to slow or prevent IPF progression; and identification and treatment of associated comorbidities to potentially improve health-related quality of life in people with IPF.
... FVC and DLCO at a given timepoint are predictive of mortality in IPF, 6,7 but do not necessarily predict future trajectory of lung function. 8,9 A substantial minority of patients with IPF are not treated with antifibrotic drugs, 10 likely related to limited or uncertain benefit, 11 patient preference or limitations on reimbursement. In summary, patients, clinicians and health care authorities may reasonably share uncertainty about the benefits of initiating treatment when lung function impairment is already severe. ...
Background and objective:
Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with idiopathic pulmonary fibrosis (IPF). However, patients with advanced IPF, as defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have not been included in randomized trials, and the outcomes of such patients who initiate treatment are not well understood. We determined lung function, disease progression and mortality outcomes following initiation of antifibrotic therapy in patients with advanced IPF at the time of treatment initiation compared to those with mild-moderate IPF.
Methods:
We included 502 patients enrolled in IPF registries from four Nordic countries. Linear mixed models were used to assess change in FVC and DLCO over time. Cox proportional hazards models were used to assess transplant-free survival and progression- and transplant-free survival.
Results:
Of 502 patients, 66 (13%) had advanced IPF. Annual change in FVC was -125 ml (95% CI -163, -87) among patients with mild-moderate IPF, and +28 ml (95% CI -96, +152) among those with advanced IPF. Advanced IPF at treatment initiation was associated with poorer transplant-free survival (hazard ratio [HR] 2.39 [95% CI 1.66, 3.43]) and progression- and transplant-free survival (HR 1.60 [95% CI 1.15, 2.23]).
Conclusion:
In a broadly representative IPF population, patients with advanced IPF at the initiation of antifibrotic therapy did not have greater lung function decline over time compared with those with mild-moderate IPF, but had substantially higher mortality. Prospective studies are needed to determine the effect of antifibrotic therapy in patients with advanced IPF.
... Progressive fibrosis with severe destructive architectural remodelling and physiological changes leads to organ malfunction and can ultimately be the cause death. Current available treatments delay the fibrotic process at most and cannot reverse or block fibrosis progression, rendering organ transplantation as the only remaining option for patients with advanced stages of fibrosis (Caminati, Cassandro, Torre, & Harari, 2017;Fan & Guan, 2016;Thabut et al., 2003). In addition, fibrosis is often diagnosed in a late phase when an organ has already lost most of its function due to excessive scarring. ...
Fibrosis is defined by excessive formation and accumulation of extracellular matrix proteins, produced by myofibroblasts, that supersedes normal wound healing responses to injury and results in progressive architectural remodelling. Fibrosis is often detected in advanced disease stages when an organ is already severely damaged and can no longer function properly. Therefore, there is an urgent need for reliable and easily detectable markers to identify and monitor fibrosis onset and progression as early as possible; this will greatly facilitate the development of novel therapeutic strategies. Osteoprotegerin (OPG), a well-known regulator of bone extracellular matrix and most studied for its role in regulating bone mass, is expressed in various organs and functions as a decoy for receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Recently, OPG has been linked to fibrosis and fibrogenesis, and has been included in a panel of markers to diagnose liver fibrosis. Multiple studies now suggest that OPG may be a general biomarker suitable for detection of fibrosis and/or monitoring the impact of fibrosis treatment. This review summarizes our current understanding of the role of OPG in fibrosis and will discuss its potential as a biomarker and/or novel therapeutic target for fibrosis.
... These two molecules decrease the progression of the disease and stabilize lung function, but unfortunately fail to halt or reverse the lung damage. [3] Lung transplantation is the only option that is seen to have survival advantage in IPF. [4] The mean numbers of years patients live after the diagnosis of IPF is 3 years, and 5-year survival rate is around 30%-35%. ...
Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease without an identifiable cause. It is the most common form of
interstitial pneumonias. The prognosis is worst in this disease with median survival of just 2–3 years after diagnosis without a lung transplant.
Currently, there are no proven medical therapies to cure IPF. Pharmacological agents such as nintedanib and pirfenidone retard the progression
of the disease to an extent but without any survival benefit. The only therapeutic option for IPF is lung transplantation with proven survival
benefit. The major concern with lung transplantation is waiting time mortality. Lung allocation score was introduced in 2005 to reduce this
mortality. Both single‑ and double‑lung transplantations are used worldwide for IPF. Bilateral lung transplantation has been seen to have
better survival rates in some studies, but there are no randomized trials which favor this recent trend. The posttransplant survival is lower than
seen in other indications for lung transplantation. Posttransplant follow‑up should be vigilant to detect complications as early as possible and
treat them accordingly.
... Presently, lung transplantation is the only viable option for IPF patients who are in a dire situation. Abundant studies on inflammatory and tissue remodeling pathways have not come out with positive outcomes due to insufficient understanding of the disease and its molecular markers (Caminati, Cassandro, Torre, & Harari, 2017). However, subsequent research in the area advocated the differential gene expression analysis comparing normal and pathogenic lung tissues (Sheu et al., 2019a,b). ...
Idiopathic pulmonary fibrosis (IPF) is a rare yet crucial persistent lung disorder that actuates scarring of lung tissues, which makes breathing difficult. Smoking, environmental pollution, and certain viral infections could initiate lung scarring. However, the molecular mechanism involved in IPF remains elusive. To develop an efficient therapeutic arsenal against IPF, it is vital to understand the pathology and deviations in biochemical pathways that lead to disorder. In this study, we availed network analysis and other computational pipelines to delineate the prominent membrane proteins as diagnostic biomarkers and therapeutic targets for IPF. This study yielded a significant role of glycosaminoglycan binding, endothelin, and GABA-B receptor signaling pathway in IPF pathogenesis. Furthermore, ADCY8, CRH, FGB, GPR17, MCHR1, NMUR1, and SAA1 genes were found to be immensely involved with IPF, and the enrichment pathway analysis suggests that most of the pathways were corresponding to membrane transport and signal transduction functionalities. This analysis could help in better understanding the molecular mechanism behind IPF to develop an efficient therapeutic target or biomarkers for IPF.
