A cohort study of interstitial lung diseases in central Denmark

Hyldgaard, Charlotte; Hilberg, Ole; Muller, Audrey; Bendstrup, Elisabeth

doi:10.1016/j.rmed.2013.09.002

Cited by 141 publications

(156 citation statements)

References 22 publications

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“…Although the clinical features are the same, NSIP is reported to have a better prognosis than iNSIP, [196]. The incidence of iNSIP is estimated to be 3 per million [197]. Clinically, NSIP is characterized by shortness of breath, and cough.…”

Section: Idiopathic Nonspecific Interstitial Pneumoniamentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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Idiopathic pulmonary fibrosis (IPF) is the most common and the most aggressive fibrosing interstitial lung disease (ILD). Despite recent promising clinical trials, IPF remains incurable and largely untreatable. Genetic studies have identified several risk loci for both sporadic and familial forms of IPF. A single variant upstream of MUC5B is predicted to account for more than 30% of all IPF risk. This variant, rs35705950, is associated with expression of MUC5B in healthy lung tissue. However, the mechanism underlying the relationship between rs35705950 and MUC5B expression remains unclear.The first goal of my thesis research was to determine whether rs35705950 is also a risk factor for other forms of ILD. Genomic DNA from individuals with IPF, HP, COPD, iNSIP, and RB-ILD was obtained and genotyped for the common MUC5B promoter variant. In these populations the risk allele was associated with IPF and iNSIP which suggested a potential shared disease mechanism. Additionally, I showed that in the IPF and control populations rs35705950 is associated with lung MUC5B expression.The second goal of my thesis research was to investigate MUC5B promoter DNA methylation which has previously been shown to play a role in MUC5B expression.Methylation analysis of the 4KB region upstream of MUC5B identified two differentially methylated regions (DMRs) associated with IPF, one DMR associated with MUC5B iv expression, and one DMR associated with rs35705950. The IPF, MUC5B expression, and rs35705950 associated DMRs are all differentially methylated at a cluster of 11 CpG motifs. overlapping DMR, including the motif disrupted by rs35705950. These findings suggest that DNA methylation may play a role in MUC5B gene regulation and IPF risk.Next, I used cross species analysis to identify highly conserved domains within the overlapping DMR. Evolutionary conservation indicated selective pressures to maintain sequences overtime and suggests biological importance. The overlapping DMR contains a highly conserved binding motif for FOXA2, a transcription factor. Further analysis using ChIP-qPCR, reporter constructs, and siRNA, established a role for FOXA2 in regulation of MUC5B expression in lung tissue. Additionally, siRNA knock down identified 3 other transcription factors which are associated with MUC5B expression; STAT3, HOXA9 and ZBTB7A. These transcriptional regulators provide insight into possible therapeutic intervention for MUC5B dysregulation and IPF.The form and content of this abstract are approved. I recommend its publication.

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Section: Idiopathic Nonspecific Interstitial Pneumoniamentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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“…In a Danish cohort, the median duration of symptoms before first visit to a referral centre was 28 months [10]. A prospective study reported a median diagnosis delay of 26 months [11].…”

Section: Introductionmentioning

confidence: 99%

The lived experience with idiopathic pulmonary fibrosis: a qualitative study

et al. 2016

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The disease course in idiopathic pulmonary fibrosis (IPF) is variable, but patients experience a progressive decline in lung function and increased symptom burden leading to death. Little is known about the patients' experience and their needs during the disease course or about the burden on family caregivers. Both patients and family caregivers face an altered life as the disease progresses. The aim of our study was to increase knowledge of life with IPF for patients and family caregivers.This study had a qualitative descriptive design using in-depth dyadic interviews with IPF patients (n=25) and family caregivers (n=24). We used the five-step analysis from the framework method and analysed the data on three levels: the patient, the family caregivers and couple level.The following six themes emerged as the main results: information and disclosure, reactional dyssynchrony, perpetual vigilance, emotional ambivalence, gradual and tacit role shift, and adapted coping strategies.Our findings suggest that IPF patients need information at the time of diagnosis, but some issues should be paced as the disease progresses. A palliation plan was demanded by patients and their caregivers. Further efforts are required to provide palliative care to IPF patients starting at the time of diagnosis. @ERSpublications IPF patients and caregivers need information, but full disclosure should be gradual and palliation initiated early

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“…However, some patients experience an accelerated decline, with acute respiratory worsening and exacerbations [12,13]. It is the type of lung fibrosis with the highest mortality rate, as the median length of survival is 3–5 years [8–11,14], which means that IPF has a poorer prognosis than a number of malignant diseases [7,15]. In 2006, Gribbin and colleagues reported a 43% 5-year survival rate among patients with IPF, and Navaratnam later estimated a 5-year survival rate of 37% in 2011 [4,16].…”

Section: Introductionmentioning

confidence: 99%

Validation of the COPD Assessment Test (CAT) in patients with idiopathic pulmonary fibrosis

Grufstedt

Shaker

Konradsen

2018

European Clinical Respiratory Journal

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Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with high morbidity and mortality. A reliable and manageable questionnaire that assesses patients’ quality of life is needed to help to improve the content of clinical consultations. The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is used in clinical practice; therefore, the aim of this study was to investigate correlations among the CAT, St. George’s Respiratory Questionnaire (SGRQ) and clinical parameters among patients diagnosed with IPF.Methods: A retrospective cohort design was employed in which 87 patients diagnosed with IPF who were receiving treatment at an outpatient clinic were included.Results: The CAT was found to be significantly correlated with SGRQ (p < 0.001). Furthermore, the CAT was significantly correlated with all of the included physiological variables.Conclusions: This add to support the validity of the COPD Assessment test (CAT) as a measure of symptoms in patients with IPF which in clinical practice in combination with dialogue between healthcare professionals and the patient, can help to improve the content of a clinical consultation.

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A cohort study of interstitial lung diseases in central Denmark

Cited by 141 publications

References 22 publications

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

The lived experience with idiopathic pulmonary fibrosis: a qualitative study

Validation of the COPD Assessment Test (CAT) in patients with idiopathic pulmonary fibrosis

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