P16‐81: The effects of fluoroquinolones on the risk of cancer in patients with interstitial disease and pulmonary fibrosis

doi:10.1111/resp.14150_990

Risk of cancer incidence in patient with idiopathic pulmonary fibrosis: An analysis of the National Health Insurance Service database of Korea

10.1183/13993003.congress-2019.pa1312 ◽

2019 ◽

Author(s):

Hong Yeul Lee ◽

Jinwoo Lee ◽

Chang-Hoon Lee ◽

Kyung-Do Han ◽

Sun Mi Choi

Keyword(s):

Health Insurance ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

National Health Insurance ◽

National Health ◽

Cancer Incidence ◽

Risk Of Cancer

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Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort

BMJ Open ◽

10.1136/bmjopen-2020-047039 ◽

2021 ◽

Vol 11 (10) ◽

pp. e047039

Author(s):

Jun-Jun Yeh ◽

Jung-Nien Lai ◽

Cheng-Li Lin ◽

Chung-Y Hsu ◽

Chia-Hung Kao

Keyword(s):

Interstitial Lung Disease ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Inhaled Corticosteroids ◽

Time Dependent ◽

Research Database ◽

Cox Models ◽

General Population Study ◽

Risk Of Cancer ◽

Statin Use

ObjectiveTo determine the effect of statins on risk of cancer in patients with interstitial lung disease (ILD) and pulmonary fibrosis.SettingWe retrospectively enrolled patients with ILD and pulmonary fibrosis and divided them into two cohorts by statin use (statin users (n=10 036) and statin non-users (n=10 036)).ParticipantsWe selected patients with ILD and pulmonary fibrosis (N=53 862) from Taiwan’s National Health Insurance Research Database. Time-dependent Cox models were used to compare risk of cancer of propensity-matched statin users and non-users. Cumulative cancer incidence was analysed through Cox proportional regression. We calculated adjusted HRs (aHRs) and their 95% CIs for cancer after adjusting for sex, age, comorbidities, and use of inhaled corticosteroids, oral steroids and statins.ResultsCompared with statin non-users, the aHRs (95% CIs) for statin users were 0.60 (0.55 to 0.65) for cancer, 0.52 (0.35 to 0.78) for haematological malignancy, 0.52 (0.38 to 0.72) for cancer of the head and neck, 0.73 (0.59 to 0.89) for colorectal cancer, 0.34 (0.26 to 0.43) for liver cancer, 0.39 (0.23 to 0.67) for pancreatic cancer, 0.40 (0.17 to 0.96) for skin cancer, 0.67 (0.52 to 0.87) for breast cancer, 0.27 (0.14 to 0.54) for cervical cancer, 0.37 (0.30 to 0.46) for other immunological cancers, 0.73 (0.54 to 0.98) for bladder/kidney cancer and 0.88 (0.71 to 1.09) for lung cancer.ConclusionStatin use is associated with lower risk of cancer in the ILD and pulmonary fibrosis cohort.

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Risk of cancer incidence in patients with idiopathic pulmonary fibrosis: A nationwide cohort study

Respirology ◽

10.1111/resp.13911 ◽

2020 ◽

Author(s):

Hong Yeul Lee ◽

Jinwoo Lee ◽

Chang‐Hoon Lee ◽

Kyungdo Han ◽

Sun Mi Choi

Keyword(s):

Cohort Study ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Cancer Incidence ◽

Risk Of Cancer

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Idiopathic pulmonary fibrosis and coronary artery disease

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2014.403 ◽

2014 ◽

Vol 9 ◽

Author(s):

Gaetano Cicchitto ◽

Valentina Musella ◽

Mario Acitorio ◽

Nicola Capuano ◽

Giuseppe Fiorenzano ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Usual Interstitial Pneumonia ◽

Careful Analysis ◽

Cardiopulmonary Exercise Test ◽

Interstitial Disease ◽

Artery Disease ◽

Careful Assessment

Idiopathic pulmonary fibrosis (IPF) is defined as a chronic fibrosing interstitial disease of unknown cause, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP); it generally progresses into respiratory failure and death. Although progression of the disease is the most common cause of death, there are increasing reports of its association with other pathologies has been reported: e.g., IPF patients seem more susceptible to cardiovascular diseases. Therefore, other pathologies might also influence the natural course. In this paper, we describe a case of IPF and coronary artery disease (CAD). We emphasize the importance of cardiopulmonary exercise test (CPET) as a useful procedure to monitor disease progression in IPF patients. We also stress the importance of a careful analysis of variables measured for an accurate interpretation of the clinical picture and an improvement of the clinical management of patients. Moreover, we suggest that a careful assessment of CPET parameters may additionally help in the early detection of high cardiovascular ischemic risk.

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Genetic variant in SPDL1 reveals novel mechanism linking pulmonary fibrosis risk and cancer protection

10.1101/2021.05.07.21255988 ◽

2021 ◽

Author(s):

Jukka T. Koskela ◽

Paavo Happola ◽

Aoxing Liu ◽

Juulia Partanen ◽

Giulio Genovese ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Telomere Length ◽

Cellular Senescence ◽

Population Sample ◽

Missense Variant ◽

Length Variation ◽

Uk Biobank ◽

Cellular Division ◽

Chromosomal Alterations ◽

Risk Of Cancer

Idiopathic Pulmonary Fibrosis (IPF) is a rare disease with poor prognosis. By contrast, cancer is common in any elderly population and a leading killer, but is now often curable. Of note, whereas IPF is driven by cellular senescence, cancer is characterized by uncontrolled cell division. Using data available from two large biobank-based studies (Finnish FinnGen study and UK biobank), we conducted a comprehensive analysis of the shared genetic background of IPF and cancer. In a population sample of 218,792 Finns with complete longitudinal health histories, we estimated the effect of individual genetic variants to the lifetime risk of IPF and cancer. We extend the analysis from IPF-GWAS to pan-cancer meta-analysis over FinnGen and UK Biobank and finally to the identification of genetic drivers of somatic chromosomal alterations. We detected six loci (SPDL1, MAD1L1, MAP2K1, RTEL1-STMN3, TERC-ACTRT3, OBFC1) associated with both IPF and cancer, all closely related to cellular division. However, each individual signal is found with opposite effects over the two diseases, termed as antagonistic pleiotropy. Several of these loci (TERC-ACTRT3, RTEL1-STMN3, OBFC1) are among the strongest inherited factors for constitutive telomere length variation and consistently indicate that shorter telomere length would increase the risk for IPF but protect from malignancy. However, a Finnish enriched SPDL1 missense variant and a common MAD1L1 intronic variant had no effect on telomere length but were shown to protect individuals from accumulation of somatic mutations. The decreased risk of cancer in SPDL1 and MAD1L1 variant carriers might result from a lower number of chromosomal alterations accumulated over time, conversely leading to fibrosis in the lung due to cellular senescence-induced inflammation. We hypothesize that the SPDL1 missense variant functions as gain-of-function mutation, leading to cellular senescence, a barrier to cancer and a driver of fibrosis in IPF. If translated to therapy, these findings might not only be able to offer relief to individuals with IPF, but also to protect from onset of cancer.

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Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162533 ◽

1996 ◽

Vol 54 ◽

pp. 14-15

Author(s):

C. G. Plopper ◽

C. Helton ◽

A. J. Weir ◽

J. A. Whitsett ◽

T. R. Korfhagen

Keyword(s):

Growth Factor ◽

Pulmonary Fibrosis ◽

Transgenic Mice ◽

Blood Vessels ◽

Lung Parenchyma ◽

Lung Maturation ◽

Alveolar Air ◽

Parenchymal Tissue ◽

Air Space ◽

Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

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