Variation in clinical approaches in the picture

SPR245 Banner 230x138 ERS int. Congress 2016During the session ‘IPF clinical’, a wide range of topics about idiopathic pulmonary fibrosis (IPF) were presented, varying from cryobiopsies, comorbid emphysema, and the risks of prednisone use. For example, a French analysis showed that FVC may be unsuitable as a measure of disease progression in patients with a combination of IPF and ≥15% emphysema.

There is increasing interest for transbronchial lung cryobiopsies (TBLCs) in the treatment of interstitial lung diseases (ILD). TBLCs are less invasive than surgical lung biopsies (SLBs) and are associated with fewer comorbidities and shorter hospitalisation time. A Belgian multicenter study, which was presented by Benjamin Bondue (Brussels, Belgium), evaluated the safety data and diagnostic yield and the added value of SLB following TBLCs when unconclusive or showing a pattern of non-specific interstitial pneumonia (NSIP). Four TBLCs were obtained from two different segments of a same lobe. All biopsies were analysed by an expert pathologist in ILDs. This study confirms that compared to SLB lung cryobiopsies reduce morbidity and hospitalisation time. If lung biopsy is required, Bondue recommends a sequential approach, composed of cryobiopsies with or without SLB.

Negative correlation
Emphysema is present in approximately one-third of patients with IPF. Hyperinflation associated with emphysema may artificially preserve FVC values. Therefore, serial FVC measurements may not capture IPF progression, which may have important implications for routine IPF monitoring and clinical trial design. In a post-hoc analysis including 455 patients from two placebo-controlled trials of interferon γ-1b in IPF (GIPF-001 and -007 trials), Vincent Cottin (Lyon, France) evaluated the relationship between the extent of emphysema, the extent of fibrosis and change in pulmonary function over 48 weeks. He found a negative correlation between the extent of fibrosis and the extent of emphysema (r=-0.232; p<0.001). According to the author, the results of this analysis have important implications for clinical trial design and monitoring of disease progression in patients with IPF. The results of this analysis may also affect countries with limited access to anti-fibrotic therapy for patients with a FVC <80%. The confounding effect of emphysema on FVC may lead to preserved FVC values that spuriously suggest limited fibrosis. The relationship between baseline fibrosis extent and FVC decline over 48 weeks is modified by baseline emphysema extent in patients with IPF. Because serial FVC measurements may not capture IPF progression, other endpoints, including DLco and CPI, should be considered.

National patient charter
A completely different topic was presented by Nicola Cassidy (Dublin, Ireland), namely results of a national patient charter (Table 1), which was developed by the Irish Lung Fibrosis Association (ILFA), the aim of which was to increase awareness of IPF and to inform patients of their entitlements for accessing optimal IPF treatment and support. The analyses were performed in five focus group meetings, with support groups, that consisted of 23 patients and 10 carers.

Table 1. Key areas and aims of the National Patient Charter for IPF.

Key areas

  • Early and accurate diagnosis
  • Communication: clear and concise information
  • Medicine and oxygen therapy
  • Pulmonary rehabilitation and exercise
  • Lung transplant assessment with minimal emphasis on age
  • Social, practical and emotional supports

  • Give patients a clear expectation of the standard of care they should receive
  • Inform patients about the medical treatment and services  to which they should have access
  • Ensure that healthcare professionals are clear on what patients expect of them

According to Cassidy, this project effectively and meaningfully engaged patients, carers and healthcare professionals, and integrated their treatment priorities into a National Patient Charter for IPF.

Comorbidities are frequent in IPF patients and affect the course of the disease. Patients with IPF have a substantial impairment in their health-related quality of life (HRQoL). Previous analyses suggest a correlation of HRQoL to dyspnoea and functional parameters.
The INSIGHTS-IPF registry, is a a multicenter, observational study in IPF expert centers across Germany, the aim of which is to describe the association between baseline characteristics, such as comorbidities and lung function, with HRQoL in a large cohort of IPF patients treated under real-life conditions. It was found that HRQoL is significantly impaired in patients with IPF. Different measures of HRQoL in patients with IPF show a significant correlation with each other. Furthermore, HRQoL correlates significantly to symptoms (NYHA), number of comorbidities, hospitalizations and disease severity. Multivariate analyses suggest that FVC, LTOT, age and symptoms significantly affect HRQoL. Also longitudinal changes in FVC are correlated with HRQoL.

No prednisone
A Dutch retrospective cohort study, which was presented by Ivo A. Wiertz (Utrecht, Netherlands), showed that prednisone could have multiple negative outcomes in patients with possible IPF. During a multidisciplinary discussion (MDD), possible IPF is divided in IPF, which is treated with anti-fibrotic drugs, and no IPF, which is treated with corticosteroids. That is, prednisone 0.5-0.15 mg/kg/day during 6 months. The 59 participants were derived from two ILD referral centers: St Antonius Hospital in Nieuwegein, the Netherlands, and UZ Leuven, Belgium.
In prednisone treated patients, Wiertz found an accelerated FVC decline and a high incidence of severe adverse events. He therefore advises caution when giving prednisone treatment to patients with possible IPF.

In the pathogenesis of IPF, next to genetic factors also environmental and host factors might be involved. Examples are smoking, wood, mineral and metal dusts, agriculture and livestock. Air pollution is associated with an increased risk of acute exacerbation of IPF.  A prospective observational registry from Belgium and Luxembourg described the disease course and outcomes of 175 IPF patients in a real-world clinical setting. Wim Wuyts (Leuven, Belgium), who presented the data, and colleagues found that exogenous factors might play a role in the pathogenesis of IPF and the progression of the disease.

Source: Session 652, IPF clinical. September 6th, 14:45-16:45, Room P.