A recent analysis of national registry data from the UK sheds light on the possible impact of biological sex on idiopathic pulmonary fibrosis. Sarah Mulholland and Dr Shaney Barratt discuss their findings, highlighting gaps in current care pathways and the growing opportunity to develop more tailored approaches to improve outcomes for people living with this condition.
Growing evidence indicates that biological sex affects the incidence, presentation, diagnosis and outcomes of many pulmonary diseases. Idiopathic pulmonary fibrosis (IPF) – a progressive fibrotic lung disease with a poor prognosis – is no exception, showing clear sex-based differences and reports of varied lived experiences among men and women.
With this in mind, we conducted the first UK analysis of national registry data specifically designed to examine sex differences in IPF, drawing on what we believe to be one of the largest real-world datasets available – the British Thoracic Society UK Interstitial Lung Disease Registry.
Established in 2013, this national multicentre observational database compiles detailed information recorded by hospital clinical teams, including clinical features, lung function, radiological patterns of pulmonary fibrosis at presentation, and subsequent treatment. Data are captured at baseline and updated every 12 months, providing a comprehensive longitudinal view of patient care.
IPF study design and outcomes
We analysed data from 7,177 enrolled patients from January 2013 to September 2023 to examine differences in baseline patient characteristics, referral symptoms, time to diagnosis and management and/or outcomes, stratifying analyses by biological sex.
The majority of patients included were male (77.8%, n=5,587) and exhibited more impaired lung function (forced vital capacity (FVC) 76.4% for males vs FVC 78.8%, p<0.001 for females) and higher Gender-Age-Physiology Index at baseline compared to females, suggesting that men may be diagnosed at a more advanced stage than women.
Furthermore, most patients had a lead time of over 12 months for exertional breathlessness and/or cough at the point of enrolment in the registry, with more females experiencing symptoms for over 24 months (40.1% vs 36.6% in males).
Taken together, these data suggest that patients continue to face barriers to timely diagnosis, underscoring the potential value of tailored health awareness campaigns.
Comorbidities varied according to biological sex, with diabetes and cardiovascular disease more statistically common in men. Gastro-oesophageal reflux disease and major depressive illness are more common in females.
Further research is needed to understand how these comorbidities influence IPF progression, symptom burden, quality of life and survival.
Mortality data were less robust, with 713 patients having complete datasets for analysis. In this group, female sex was associated with longer survival. Multivariate analysis identified male sex, older age, lower baseline FVC% predicted and the presence of coexistent lung cancer as independent predictors of poorer survival.
Uptake of antifibrotic therapies
Our data also found that, while males were more likely to meet criteria for antifibrotic prescribing at baseline, a significant proportion declined to take medication by personal choice. This was significantly higher among males than among females (47.0% vs 29.6%).
Determining factors that influence antifibrotic uptake in this group requires further research. However, strategies such as using tools that facilitate shared decision-making to improve patient ‘buy-in’ and confidence in their medication, along with culturally sensitive counselling tailored to patient beliefs and health literacy, may help to increase uptake and improve personalised care and education.
While these population-level findings may provide useful context for risk stratification discussions, they should not alter monitoring or treatment decisions for individual patients. The pronounced disparity in life expectancy among males across a range of diseases, including in IPF, has contributed to calls for a national men’s health strategy in the UK.
Exercising caution when interpreting registry data
Registries play a pivotal role in furthering our understanding of disease characteristics and disease behaviour over time. However, when interpreting these registry-based, population-level findings, it is important to recognise that much of the data originates from tertiary care settings and therefore should be approached with caution due to potential selection bias.
Furthermore, data entry for the Interstitial Lung Disease Registry is currently reliant on local resource allocation, which may not be sustainable in some organisations and may compromise data robustness. Linking registry data with hospital and national mortality datasets in the future could strengthen data quality and further drive personalised patient care.
Our further planned work will explore sex-specific differences in adherence, tolerability and safety of antifibrotic therapies.
From insight to action in IPF
Only through understanding these differences can we begin to develop strategies to address them.
Dose adjustments, antifibrotic switching, amending timing of medication, and discussion of beliefs or concerns that have resulted in reduced adherence, are all strategies currently employed by our multidisciplinary team in the routine management of antifibrotic therapies.
Knowledge of sex-differences may enable us to tailor our patient education and support to further improve adherence and patient quality of life in this cohort. Moreover, future clinical trials should prioritise the reporting of sex-disaggregated data to drive personalised approaches to IPF management.
Authors
Sarah Mulholland MPharm
Lead pharmacist – respiratory medicine, North Bristol NHS Trust, UK
Dr Shaney Barratt MBBS PhD
Honorary associate professor in respiratory medicine, University of Bristol, and respiratory consultant, Bristol Interstitial Lung Disease Service, North Bristol NHS Trust, UK
This article was originally published by our sister publication Hospital Pharmacy Europe.