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.

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.

Palliative care in interstitial lung disease: living well.

Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise.

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. TRIAL REGISTRATION: The INSIGHTS-IPF registry is registered at Clinicaltrials.gov ( NCT01695408 ).

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

RATIONALE: Health-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Little is understood about HRQL in specific subtypes of ILD. OBJECTIVES: The 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). METHODS: We 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 RESULTS: RA-ILD patients (n = 50) were more likely to be younger and female compared to IPF patients (n = 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 = 0.03), with significant differences in two of four PCS domains - bodily pain (P < 0.01) and general health (P = 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 < 0.01). Mental and emotional health, as measured by the MCS, was similar between RA-ILD and IPF patients. CONCLUSION: The 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.

The need for patient-centred clinical research in idiopathic pulmonary fibrosis.

Patient-centredness is an accepted term and is perceived by healthcare professionals to be morally and ethically desirable. We are motivated by the belief that this approach will improve the patient-professional experience of the decision-making process and improve health outcomes. We acknowledge that patients, either as participants or as co-investigators, have positive contributions to make to research. As the idiopathic pulmonary fibrosis (IPF) community enters a new era of clinical research activity we consider that there is greater capacity for patient involvement and partnership.Patient involvement in research can be optimised through collaborations in the research design, study conduct, and dissemination. There is increasing interest in using patient- reported outcomes (PROs), such as health-related quality of life, and symptoms measures to inform decision-making and ensure patient perspectives are taken into account. PROs are an essential component of specialist IPF services, to monitor and improve care delivery and to measure and benchmark performance. In clinical trials, PROs can additionally be used to define entry criteria, evaluate efficacy of an intervention, and evaluate adverse events. We suggest that there is a much wider scope for including patient-centred PROs in clinical research and for creative thought in developing patient co-investigator roles.Participation in research activity requires highly refined decision-making processes, particularly in a condition such as IPF, which has an often unpredictable trajectory. The IPF research landscape has changed and the design and conduct of clinical trials in IPF requires some radical rethinking. It is accepted that involving patients in the role of co-investigators will impact the research questions we ask and result in study designs that are patient-centred. IPF clinical trials have been hindered by the lack of availability of validated, disease-specific questionnaires. A conservative approach appears to have been taken to the inclusion of generic symptom or quality of life measures as PRO endpoints. Thus, the impact of new drugs on the quality of life of research participants demonstrates only minimal benefit. It is time to refocus on a patient-centred approach with regards to the co-investigator role, PRO development, and research participants.

Benefits of physical training in patients with idiopathic or end-stage sarcoidosis-related pulmonary fibrosis: a pilot study.

BACKGROUND: The natural history of disease in patients with stage IV (fibrotic) sarcoidosis may mirror that of patients with idiopathic pulmonary fibrosis (IPF). Both are bothered by progressive dyspnea, exercise limitation and fatigue. OBJECTIVE: To establish whether patients suffering from pulmonary fibrosis might benefit from a physical training program. STUDY DESIGN: Twenty-four eligible patients referred to the out-patient clinic of the ild care expertise team of Hospital Gelderse Vallei, Ede, The Netherlands between November 2012 and November 2013 were included in this observational pilot study of a 12-week physical training program. Outcomes, including exercise capacity, skeletal muscle strength, lung function and fatigue were assessed at two time points: 1) baseline; and 2) after completion of a 12-week physical training program. RESULTS: At baseline, the percentage predicted DLCO, FVC, FEV1 and exercise capacity (assessed by six-minute walking distance (6MWD) or maximal oxygen uptake) was reduced in both groups. After program completion, exercise capacity improved (>10% improvement 6MWD) in 13 subjects (54.2%): 7 with IPF and 6 with sarcoidosis subjects. Other secondary endpoints, including pulmonary function tests and patient-reported outcome measures improved in some subjects. CONCLUSION: A 12-week physical training program improved or maintained exercise capacity in patients with IPF (despite disease progression) or fibrotic sarcoidosis. The results from this pilot study could be used to design prospective studies aimed at answering lingering questions about exercise training in patients with these progressive, incurable conditions.

Benefits of Physical Training in Sarcoidosis.

BACKGROUND: Sarcoidosis patients suffer from fatigue and exercise limitation. The aim of this study was to establish whether a physical training program improves these and other outcomes important to sarcoidosis patients. METHODS: From 11/2012 to 9/2014, 201 sarcoidosis patients were referred to the ild care expertise team, Ede, the Netherlands. In our center, all patients are routinely recommended to undergo testing at baseline to determine their physical functioning and encouraged to complete a 12-week, supervised physical training program. Ninety patients underwent baseline testing and returned for repeat testing at 3 months in the interim, 49 completed the training program (Group I) and 41 chose not to participate (Group II). Change over time (from baseline to 3 months) in fatigue, exercise capacity, and skeletal muscle strength were assessed between the two groups. RESULTS: At baseline, there were no between-group differences for fatigue, DLCO%, FVC%, or exercise capacity [assessed by percent predicted six-minute walk distance (6MWD%) and Steep Ramp Test (SRT)]. The 6MWD for Group I improved between baseline and 3 months, while the 6MWD remained the same in Group II (F = 72.2, p < 0.001). Group I showed a significantly larger decrease of fatigue compared with Group II (F = 6.27, p = 0.014). Lung function tests did not change in either group. CONCLUSION: A supervised physical training program improves exercise capacity and fatigue among sarcoidosis patients and should be included in their management regimen.

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, St. George's Respiratory Questionnaire (SGRQ), and Medical Research Council scale. Confirmatory factor analysis confirmed the two-component structure of the D-12 (i.e., seven items that tap the physical aspects of breathlessness and five 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 Medical Research Council grade (r = 0.636), while the affective component was more strongly correlated with SGRQ Impacts (r = 0.765) and Hospital Anxiety and Depression scale 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.

High-resolution chest tomography in idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia: utility and challenges.

PURPOSE OF REVIEW: High-resolution computed tomography (HRCT) scan is regarded as the imaging modality of choice to evaluate patients with known or suspected interstitial lung disease. With current technology, HRCT allows for detailed assessment of interstitial compartments. We examine recent data on its role in the diagnostic evaluation, clinical decision-making, and prognosis of patients with interstitial lung disease, and we highlight the challenges related to its application in this field. RECENT FINDINGS: HRCT findings are either diagnostic or strongly suggestive of underlying pathologic patterns. By identifying the presence of certain characteristics, radiologists have developed a clearer understanding of HRCT patterns that coincide with underlying pathology. Challenges and controversies still remain, however. For example, recent studies indicate that the diagnostic accuracy and performance characteristics of HRCT depend predominantly on the study setting; intra-observer and inter-observer variability are less between academic radiologists than between community radiologists. Despite this, clinicians tend to rely primarily on HRCT when a radiologic pattern characteristic for histologic usual interstitial pneumonia is identified. SUMMARY: Specific HRCT patterns help to differentiate and prognosticate different interstitial lung diseases. It is important for clinicians to understand the utility and limitations of HRCT in managing their patients. A multidisciplinary approach remains the gold standard.