Spectrum of Fibrotic Lung Diseases

Salvati, Lorenzo; Palterer, Boaz; Parronchi, Paola

doi:10.1056/nejmc2031135

Cited by 283 publications

(16 citation statements)

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“…Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia and idiopathic fibrotic lung disorder. IPF occurs primarily in middle-aged and older adults, typically in the sixth and seventh decades, and its incidence increases remarkably with age [ 4 , 5 , 6 ]. Increased age in combination with interstitial findings on high-resolution computed tomography (HRCT) of the chest are strong predictors of IPF [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Increased age in combination with interstitial findings on high-resolution computed tomography (HRCT) of the chest are strong predictors of IPF [ 7 ]. More men than women have IPF, with a sex ratio of 7:3 [ 4 , 5 , 6 , 8 ]. Hutchinson et al estimated a conservative incidence range of 3–9 cases per 100,000 for Europe and North America [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Fibrosis results in impaired ventilation, functional respiratory impairment, reduced gas exchange, and respiratory failure [ 1 ]. IPF is characterized by a chronic, progressive, irreversible, and usually lethal clinical course [ 1 , 2 , 3 , 4 , 5 , 6 , 11 ]. Most patients have respiratory symptoms, such as coughing and dyspnea on exertion, and develop worsening pulmonary function and show progressive fibrosis on HRCT over years [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Most patients have respiratory symptoms, such as coughing and dyspnea on exertion, and develop worsening pulmonary function and show progressive fibrosis on HRCT over years [ 4 , 5 ]. IPF patients have diverse and unpredictable clinical courses and the median survival is 2.5–3.5 years after diagnosis [ 4 , 5 , 6 , 8 ]. Unfortunately, the condition of most patients worsens in the years following diagnosis and they die from acute exacerbation, progression of chronic respiratory failure, and lung cancer [ 4 , 5 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…The diagnostic criteria for idiopathic interstitial pneumonias and IPF have changed several times [ 1 , 5 , 12 ], and those for IPF were revised recently [ 12 ] to emphasize the significance of either radiological, histopathological, or in combination, features or patterns of usual interstitial pneumonia (UIP) [ 6 , 12 ]. Chest HRCT is the imaging test of choice and is regarded as an essential examination for a diagnosis of IPF [ 2 , 4 , 5 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway

Inui

Sakai

Kitagawa

2021

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. During the past decade, novel pathogenic mechanisms of IPF have been elucidated that have shifted the concept of IPF from an inflammatory-driven to an epithelial-driven disease. Dysregulated repair responses induced by recurrent epithelial cell damage and excessive extracellular matrix accumulation result in pulmonary fibrosis. Although there is currently no curative therapy for IPF, two medications, pirfenidone and nintedanib, have been introduced based on understanding the pathogenesis of the disease. In this review, we discuss advances in understanding IPF pathogenesis, highlighting epithelial–mesenchymal transition (EMT), the ubiquitin-proteasome system, and endothelial cells. TGF-β is a central regulator involved in EMT and pulmonary fibrosis. HECT-, RING finger-, and U-box-type E3 ubiquitin ligases regulate TGF-β-Smad pathway-mediated EMT via the ubiquitin-proteasome pathway. p27 degradation mediated by the SCF-type E3 ligase, Skp2, contributes to the progression of pulmonary fibrosis by promotion of either mesenchymal fibroblast proliferation, EMT, or both. In addition to fibroblasts as key effector cells in myofibroblast differentiation and extracellular matrix deposition, endothelial cells also play a role in the processes of IPF. Endothelial cells can transform into myofibroblasts; therefore, endothelial–mesenchymal transition can be another source of myofibroblasts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway

Inui

Sakai

Kitagawa

2021

IJMS

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Diagnosis and Treatment of Combined Pulmonary Fibrosis and Emphysema in 2022

Nemoto

Koo

Ryu

2022

JAMA

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Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults

et al. 2023

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ImportancePulmonary fibrosis (PF) is characterized by progressive scarring of lung tissue and poor survival. Racial and ethnic minority populations face the greatest risk of morbidity and mortality from disparities impacting respiratory health, but the pattern of age at clinically relevant outcomes across diverse racial and ethnic populations with PF is unknown.ObjectiveTo compare the age at PF-related outcomes and the heterogeneity in survival patterns among Hispanic, non-Hispanic Black, and non-Hispanic White participants.Design, Setting, and ParticipantsThis cohort study included adult patients with a PF diagnosis and used data from prospective clinical registries: the Pulmonary Fibrosis Foundation Registry (PFFR) for the primary cohort and registries from 4 geographically distinct tertiary hospitals in the US for the external multicenter validation (EMV) cohort. Patients were followed between January 2003 and April 2021.ExposuresRace and ethnicity comparisons between Black, Hispanic, and White participants with PF.Main Outcomes and MeasuresAge and sex distribution of participants were measured at the time of study enrollment. All-cause mortality and age at PF diagnosis, hospitalization, lung transplant, and death were assessed in participants over 14 389 person-years. Differences between racial and ethnic groups were compared using Wilcoxon rank sum tests, Bartlett 1-way analysis of variance, and χ2 tests, and crude mortality rates and rate ratios were assessed across racial and ethnic categories using Cox proportional hazards regression models.ResultsIn total, 4792 participants with PF were assessed (mean [SD] age, 66.1 [11.2] years; 2779 [58.0%] male; 488 [10.2%] Black, 319 [6.7%] Hispanic, and 3985 [83.2%] White); 1904 were in the PFFR and 2888 in the EMV cohort. Black patients with PF were consistently younger than White patients (mean [SD] age at baseline, 57.9 [12.0] vs 68.6 [9.6] years; P &lt; .001). Hispanic and White patients were predominantly male (Hispanic: PFFR, 73 of 124 [58.9%] and EMV, 109 of 195 [55.9%]; and White: PFFR, 1090 of 1675 [65.1%] and EMV, 1373 of 2310 [59.4%]), while Black patients were less likely to be male (PFFR, 32 of 105 [30.5%] and EMV, 102 of 383 [26.6%]). Compared with White patients, Black patients had a lower crude mortality rate ratio (0.57 [95% CI, 0.31-0.97), but for Hispanic patients, the mortality rate ratio was similar to that of White patients (0.89; 95% CI, 0.57-1.35). Mean (SD) hospitalization events per person were highest among Black patients compared with Hispanic and White patients (Black: 3.6 [5.0]; Hispanic, 1.8 [1.4]; and White, 1.7 [1.3]; P &lt; .001). Black patients were consistently younger than Hispanic and White patients at first hospitalization (mean [SD] age: Black, 59.4 [11.7] years; Hispanic, 67.5 [9.8] years; and White, 70.0 [9.3] years; P &lt; .001), lung transplant (Black, 58.6 [8.6] years; Hispanic, 60.5 [6.1] years; and White, 66.9 [6.7] years; P &lt; .001), and death (Black, 68.7 [8.4] years; Hispanic, 72.9 [7.6] years; and White, 73.5 [8.7] years; P &lt; .001). These findings remained consistent in the replication cohort and in sensitivity analyses within prespecified deciles of age groups.Conclusions and RelevanceIn this cohort study of participants with PF, racial and ethnic disparities, especially among Black patients, were found in PF-related outcomes, including earlier onset of death. Further research is essential to identify and mitigate the underlying responsible factors.

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Spectrum of Fibrotic Lung Diseases

Cited by 283 publications

References 12 publications

Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway

Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway

Diagnosis and Treatment of Combined Pulmonary Fibrosis and Emphysema in 2022

Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults

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