The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry

Background: Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry. Methods: Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DLCO% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DLCO % predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DLCO. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations. Conclusions: QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality

Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry

Background: The INSIGHTS-IPF registry provides one of the largest data sets of clinical data and self-reported patient related outcomes including health related quality of life (QoL) on patients with idiopathic pulmonary fibrosis (IPF). We aimed to describe associations of various QoL instruments between each other and with patient characteristics at baseline. Methods: Six hundred twenty-three IPF patients with available QoL data (St George's Respiratory Questionnaire SGRQ, UCSD Shortness-of-Breath Questionnaire SoB, EuroQol visual analogue scale and index EQ-5D, Well-being Index WHO-5) were analysed. Mean age was 69.6 +/- 8.7 years, 77% were males, mean disease duration 2.0 +/- 3.3 years, FVC pred was 67.5 +/- 17.8%, DLCO pred 35.6 +/- 17%. Results: Mean points were SGRQ total 48.3, UCSD SoB 47.8, EQ-5D VAS 66.8, and WHO-5 13.9. These instruments had a high or very high correlation (exception WHO-5 to EQ-5D VAS with moderate correlation). On bivariate analysis, QoL by SGRQ total was statistically significantly associated with clinical symptoms (NYHA;p < 0.001), number of comorbidities (p < 0.05), hospitalisation rate (p < 0.01) and disease severity (as measured by GAP score, CPI, FVC and 6-min walk test;p < 0.05 each). Multivariate analyses showed a significant association between QoL (by SGRQ total) and IPF duration, FVC, age, NYHA class and indication for long-term oxygen treatment. Conclusions: Overall, IPF patients under real-life conditions have lower QoL compared to those in clinical studies. There is a meaningful relationship between QoL and various patient characteristics

High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis

Assessment of dyspnea in asthma: Validation of the dyspnea-12

BACKGROUND: Dyspnea is a prominent symptom in asthma. The Dyspnea-12 (D-12), an instrument that quantifies breathlessness using 12 descriptors that tap the physical and affective aspects, has shown promise for the measurement of dyspnea in cardiorespiratory disease. OBJECTIVE: We report the results of a study designed to test the validity and reliability of the D-12 in a population of patients with asthma. METHODS: This cross-sectional study included 102 patients with asthma. Subjects completed the D-12, Hospital Anxiety and Depression Scale (HAD), St George’s Respiratory Questionnaire (SGRQ), MRC scale. Confirmatory factor analysis confirmed the two-component structure of the D-12 (i.e. 7 items that tap the Physical aspects of breathlessness and 5 items that tap the Affective aspects). RESULTS: The D-12 subscales had excellent internal reliability (Cronbach’s alpha for the ‘Physical’ score was 0.94 and the Affective score was 0.95). The D-12 Physical component was more strongly correlated with SGRQ Symptoms (r = 0.648), SGRQ Activities (r = 0.635) and MRC grade (r = 0.636), while the Affective component was more strongly correlated with SGRQ Impacts (r = 0.765) and HAD scores (anxiety r = 0.641 and depression r = 0.602). CONCLUSION: This study supports validity of the D-12 for use in the assessment of dyspnea of patients with asthma. It assesses one of the most pertinent symptoms of asthma from two viewpoints -physical and affective

Understanding the determinants of health-related quality of life in rheumatoid arthritis-associated interstitial lung disease

RationaleHealth-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Little is understood about HRQL in specific subtypes of ILD.ObjectivesThe aim of this study was to characterize and identify clinical determinants of HRQL among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and compare them to patients with idiopathic pulmonary fibrosis (IPF).MethodsWe identified patients with a diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients. HRQL was measured at their baseline visit using the Short Form Health Survey (SF-36), versions 1 and 2. Regression models were used to characterize and understand the relationship between selected baseline clinical covariates, the physical component score (PCS) and mental component score (MCS) of the SF-36.Measurements and main resultsRA-ILD patients (n&nbsp;=&nbsp;50) were more likely to be younger and female compared to IPF patients (n&nbsp;=&nbsp;50). After controlling for age and pulmonary function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured by the PCS (P&nbsp;=&nbsp;0.03), with significant differences in two of four PCS domains - bodily pain (P&nbsp;&lt;&nbsp;0.01) and general health (P&nbsp;=&nbsp;0.01). Clinical covariates most strongly associated with a lower PCS in RA-ILD patients compared to IPF patients were the presence of joint pain or stiffness and dyspnea severity (P&nbsp;&lt;&nbsp;0.01). Mental and emotional health, as measured by the MCS, was similar between RA-ILD and IPF patients.ConclusionThe physical components of HRQL appear worse in RA-ILD patients compared to IPF patients as measured by the PCS of the SF-36. Differences in the PCS of the SF-36 can be explained in part by dyspnea severity and joint symptoms among patients with RA-ILD

Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function

This post hoc analysis examined the differences in idiopathic pulmonary fibrosis disease progression and the effects of pirfenidone in patients stratified by more preserved versus less preserved baseline lung function status using forced vital capacity (FVC) or GAP (gender, age and physiology) index stage.Efficacy outcomes, i.e. FVC, 6-min walking distance (6MWD) and dyspnoea (University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)), were analysed at 12 months in patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the pooled phase 3 CAPACITY/ASCEND population (n=1247), with subgroups stratified by baseline FVC ≥80% versus <80% or GAP stage I versus II-III. Treatment-by-subgroup interaction was tested based on a rank ANCOVA model; factors in the model included study, region, treatment, subgroup and treatment-by-subgroup interaction term.Patients with both more preserved (FVC ≥80% or GAP stage I) and less preserved (FVC <80% or GAP stage II-III) lung function at baseline demonstrated clinically significant disease progression at 12 months in terms of categorical decline in FVC, 6MWD and UCSD SOBQ. The magnitude of pirfenidone treatment effect was comparable between subgroups, regardless of whether lung function was classified using FVC or GAP index stage.These findings support the initiation of treatment with pirfenidone, irrespective of stage of baseline lung function in this patient population

Developing a conceptual model of symptoms and impacts in progressive fibrosing interstitial lung disease to evaluate patient-reported outcome measures

Background An understanding of the experience of patients with progressive fibrosing interstitial lung disease (PF-ILD) is needed to select appropriate patient-reported outcome measures (PROMs) to evaluate treatment effect in clinical trials. Methods A systematic literature review was conducted to develop a preliminary conceptual model of the symptoms experienced by patients with PF-ILD and the impacts the disease has on them. An online survey and consensus meetings were then conducted with 12-14 stakeholders (patients, clinicians, regulatory and payer advisors) to refine the conceptual model and critically appraise how key concepts should be measured by PROMs. PROMs assessed included Living with Idiopathic Pulmonary Fibrosis, Living with Pulmonary Fibrosis, the King's Brief Interstitial Lung Disease questionnaire, Cough and Sputum Assessment Questionnaire, Evaluating Respiratory Symptoms, Leicester Cough Questionnaire, Functional Assessment of Chronic Illness Therapy (Dyspnoea/Fatigue) and St George's Respiratory Questionnaire for Idiopathic Pulmonary Fibrosis. Results The literature review identified 36 signs/symptoms and 43 impacts directly or indirectly related to pulmonary aspects of PF-ILD. The most relevant symptoms identified by participants included shortness of breath on exertion, fatigue and cough; relevant impacts included effects on physical functioning, activities of daily living and emotional wellbeing. These are presented in a conceptual model. Consensus opinion was that existing PROMs need further modification and validation before use in clinical trials. Conclusions The conceptual model improves understanding of the symptoms and impacts that living with PF-ILD has on patients' wellbeing. It can help to inform the choice of PROMs in clinical trials and highlight aspects to assess in the clinical care of patients with PF-ILD