Dataset Information

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore.

ABSTRACT:

Background

Non-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.

Methods

F-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).

Results

Four clusters were identified. Cluster 1 (n=53, 26.4%) comprised older Chinese males with high body mass index (BMI) and comorbidity burden, higher baseline forced vital capacity (FVC) percentage predicted and lower diffusing capacity of the lung for carbon monoxide (DLCO) percentage predicted. They had similar mortality to IPF. Cluster 2 (n=67, 33.3%) had younger female non-smokers with low comorbidity burden, groundglass changes on high-resolution chest computed tomography (HRCT) and a positive anti-nuclear antibody (ANA) titre ≥1:160. They had lower baseline FVC and higher DLCO, low mortality and slower lung function decline. Cluster 3 (n=42, 20.9%) consisted male smokers with low comorbidity burden, emphysema on HRCT and high baseline lung function. They had low mortality and slow lung function decline. Cluster 4 (n=39, 19.4%) was the highest risk and comprised of mainly Indians with high BMI. They had the highest proportion of ischemic heart disease (IHD) and previous pulmonary tuberculosis. Subjects had the lowest baseline lung function, highest mortality, and fastest lung function decline. Survival differences across clusters remained significant following adjustment for treatment.

Conclusions

We identified four distinct F-ILD clinical phenotypes with varying disease trajectories. This demonstrates heterogeneity in F-ILD and the need for complementary approaches for classification and prognostication beyond ATS/ERS guideline diagnosis.

SUBMITTER: Kam MLW

PROVIDER: S-EPMC9344411 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore.

Kam Michelle Li Wei MLW Tiew Pei Yee PY Chai Hui Zhong HZ Low Su Ying SY

Journal of thoracic disease 20220701 7

<h4>Background</h4>Non-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.<h4>Methods</h4>F-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).<h4>Results</h4>Four clusters were identified. Cluster 1 (n=53, 2 ...[more]

PMID: 35928611

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Project description:BackgroundCough remains a persistent symptom in patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). To inform future research, treatment and care models, we conducted the first systematic synthesis of evidence on its associated burden.MethodsA literature search was performed for articles published between January 2010 and October 2023 using databases including Embase, MEDLINE and the Cochrane Library. Studies in patients with IPF and other ILDs reporting cough-related measures were eligible for inclusion. Included studies were categorised based on the types of ILD they examined and their design. Study details, patient characteristics and outcomes were extracted, and the risk of bias was assessed. A narrative synthesis approach was employed to interpret the findings.ResultsSixty-one studies were included: 33 in IPF, 18 in mixed-ILDs, six in connective tissue disease-associated-ILDs and four in sarcoidosis. Across the studies, a range of tools to assess cough and its impact were used. The most frequently used measures of cough were cough severity visual analogue scale (VAS) and objective cough counts, whereas the most frequently used health-related quality of life (HRQoL)/impact measures were the St. George's Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ). In IPF, studies consistently reported correlations between various cough and HRQoL measures, including between cough VAS scores and objective cough counts, LCQ scores and SGRQ scores. Similar correlations were observed in studies in other ILDs, but data were more limited. Qualitative studies in both IPF and other ILDs consistently highlighted the significant cough-related burden experienced by patients, including disruption of daily activities, fatigue and social embarrassment. Although there were no studies specifically investigating the economic burden of cough, one study in patients with fibrotic ILD found cough severity was associated with workplace productivity loss.ConclusionsOur study underscores the heterogeneity in assessing cough and its impact in IPF and other ILDs. The findings confirm the negative impact of cough on HRQoL in IPF and suggest a comparable impact in other ILDs. Our synthesis highlights the need for standardised assessment tools, along with dedicated studies, particularly in non-IPF ILDs and on the economic burden of cough.

Project description:Differences in the organisation of idiopathic pulmonary fibrosis (IPF) and interstitial lung diseases (ILDs) in the Nordic countries are not well described. Diagnostic setups, treatment modalities and follow-up plans may vary due to national, cultural and epidemiological features. The aim of the present study was to describe the different organisation of diagnostics and treatment of IPF and ILD in the Nordic countries. All university and regional hospitals with respiratory physicians were invited to respond to a questionnaire collecting data on the number of physicians, nurses, patients with ILD/IPF, the presence of and adherence to disease-specific national and international guidelines, diagnosis and treatment including ILD-specific palliation and rehabilitation programmes. Twenty-four university and 22 regional hospitals returned the questionnaire. ILD and IPF incidence varied between 1.4 and 20/100,000 and 0.4 and 10/100,000, respectively. Denmark and Estonia have official national plans for the organisation of ILD. The majority of patients are managed at the university hospitals. The regional hospitals each manage 46 (5-200) patients with ILD and 10 (0-20) patients with IPF. There are from one to four ILD centres in each country with a median of two ILD specialists employed. Specialised ILD nurses are present in nine hospitals. None of the Nordic countries have national guidelines made by health authorities. The respiratory societies in Sweden, Norway and Denmark have developed national guidelines. All hospitals except two use the ATS/ERS/JRS/ALAT IPF guidelines from 2011. The limited number of ILD specialists, ILD-specialised radiologists and pathologists and the low volume of ILD centres were perceived as bottlenecks for implementation of guidelines. Twenty of the 24 university hospitals have multidisciplinary conferences (MDCs). Pulmonologists and radiologists take part in all MDCs while pathologists only participate at 17 hospitals. Prescription of pirfenidone is performed by all university hospitals except in Estonia. Triple therapy with steroid, azathioprine and N-acetylcysteine is not used. No hospitals have specific palliation programmes for patients with ILD/IPF, but 36 hospitals have the possibility of referring patients for palliative care, mostly based on existing oncology palliative care teams; seven hospitals have rehabilitation programmes for ILD. There are obvious differences between the organisations of ILD patients in the Nordic countries. We call for national plans that consider the challenge of cultural and geographical differences and suggest the establishment of national reference centres and satellite collaborative hospitals to enable development of common guidelines for diagnostics, therapy and palliation in this patient group.

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Project description:Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.

Dataset Information

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore.

Background

Methods

Results

Conclusions

Publications

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore.

Similar Datasets

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