Fibroblast activation protein and disease severity, progression, and survival in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis in the lungs. Activated fibroblasts play a central role in fibrogenesis and express fibroblast activation protein α. A truncated, soluble form (sFAP) can be measured in blood and is a potential novel biomarker of disease activity. The aim was to study the association between sFAP and clinical, radiological, and histopathological measures of disease severity, progression, and survival in a prospective, multicentre, real-world cohort of patients with IPF. Patients with IPF were recruited from the tertiary interstitial lung disease centres in Denmark and followed for up to 3 years. Baseline serum levels of sFAP were measured by ELISA in patients with IPF and compared to healthy controls. Pulmonary function tests, 6-minute walk test and quality of life measures were performed at baseline and during follow-up. The study included 149 patients with IPF. Median sFAP in IPF was 49.6 ng/mL (IQR: 43.1-61.6 ng/mL) and in healthy controls 73.8 ng/mL (IQR: 62.1-92.0 ng/mL). Continuous sFAP was not associated with disease severity, progression or survival (p > 0.05). After dichotomization of sFAP below or above mean sFAP + 2 SD for healthy controls, higher levels of sFAP were associated with lower FVC % predicted during follow-up (p < 0.01). Higher than normal serum levels of sFAP were associated with longitudinal changes in FVC % predicted, but sFAP did not show clear associations with other baseline or longitudinal parameters. As such, sFAP has limited use as a biomarker of disease progression or survival in patients with IPF.

The fibroblast hormone endotrophin is a biomarker of mortality in chronic diseases.

Fibrosis, driven by fibroblast activities, is an important contributor to morbidity and mortality in most chronic diseases. Endotrophin, a signaling molecule derived from processing of type VI collagen by highly activated fibroblasts, is involved in fibrotic tissue remodeling. Circulating levels of endotrophin have been associated with an increased risk of mortality in multiple chronic diseases. We conducted a systematic literature review collecting evidence from original papers published between 2012 and January 2023 that reported associations between circulating endotrophin (PRO-C6) and mortality. Cohorts with data available to the study authors were included in an Individual Patient Data (IPD) meta-analysis that evaluated the association of PRO-C6 with mortality (PROSPERO registration number: CRD42023340215) after adjustment for age, sex and BMI, where available. In the IPD meta-analysis including sixteen cohorts of patients with different non-communicable chronic diseases (NCCDs) (N=15,205) the estimated summary hazard ratio for 3-years all-cause mortality was 2.10 (95% CI 1.75-2.52) for a 2-fold increase in PRO-C6, with some heterogeneity observed between the studies (I2=70%). This meta-analysis is the first study documenting that fibroblast activities, as quantified by circulating endotrophin, are independently associated with mortality across a broad range of NCCDs. This indicates that, irrespective of disease, interstitial tissue remodeling, and consequently fibroblast activities, has a central role in adverse clinical outcomes, and should be considered with urgency from drug developers as a target to treat.

Identification and management of interstitial lung abnormalities.

Interstitial lung abnormalities (ILA) are incidentally observed specific CT findings in patients without clinical suspicion of interstitial lung disease (ILD). ILA with basal and peripheral predominance and features suggestive of fibrosis in more than 5% of any part of the lung should be referred for pulmonologist review. The strategy for monitoring as described in this review is based on clinical and radiological risk factors. ILA are associated with risk of progression to ILD and increased mortality. Early identification and assessment of risk factors for progression are essential to improve outcome.

Acute exacerbation of fibrotic interstitial lung diseases.

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and other fibrotic interstitial lung diseases (AE-ILD) is defined by significant acute respiratory worsening and new widespread alveolar damage. This review summarises the current knowledge of diagnosis and treatment of these events. The diagnosis of AE-IPF and AE-ILD is based on typical HRCT findings of new and bilateral ground glass opacification and/or consolidation, and exclusion of fluid overload or cardiac failure. Treatment relies, despite low quality of evidence, on glucocorticoid in addition to supportive and palliative treatment. Despite treatment, the prognosis is poor, with a median survival of 2-4 months.

Comorbidity and mortality in systemic sclerosis and matched controls: Impact of interstitial lung disease. A population based cohort study based on health registry data.

OBJECTIVE: This population-based, matched cohort study evaluates the impact of comorbidities on mortality among systemic sclerosis (SSc) patients with and without interstitial lung disease (ILD). METHOD: Patients with a first-time SSc diagnosis between 2002 and 2015 were identified in the Danish National Patient Registry, separated into two cohorts - with ILD (SSc-ILD) and without ILD (non-ILD SSc), and matched 1:4 with controls from the general population on age, sex, residency and marital status. Comorbidity and mortality data were obtained from national registries. The Deyo-Charlson comorbidity score (DCcs) was used for assessment of the burden of comorbidities. RESULTS: 1732 patients with SSc and 6919 controls were included; 258 (14.9%) patients had SSc-ILD. The hazard ratio (HR) for death was 2.8 (95% CI 2.4-3.3) in SSc, and especially increased in SSc-ILD (HR 4.2 (95% CI 3.2-5.4)), males (HR 3.1 95% CI 2.4-4.1) and younger adults (aged 18-40 (HR 6.9, 95% CI 3.4-14.2) and 41-50 (HR 7.7, 95% CI 3.8-15.6)). In non-ILD SSc, mortality increased with increasing DCcs. Cancer was the most frequent cause of death in SSc (24.9% of deaths) and in controls (33.5%), in SSc followed by musculoskeletal and connective tissue diseases (22.7%); the cause of only 0.8% of deaths among controls. CONCLUSION: The high prevalence of comorbidities in SSc had extensive impact on mortality. Mortality was increased in males, in young adults and in SSc-ILD, underlining the excess mortality associated with ILD. These findings emphasise the importance of timely diagnosis and optimal management of organ involvement and comorbidities in SSc.

[Pulmonary manifestations in rheumatoid arthritis].

Rheumatoid arthritis (RA) affects more than 30,000 Danes. In this review, we discuss RA in connection with chronic obstructive pulmonary disease (COPD), bronchiectasis and interstitial lung disease (ILD) which are among the most common lung manifestations and are associated with increased mortality. Early suspicion based upon respiratory symptoms should prompt imaging and pulmonary function test. Smoking cessation, vaccination, and rehabilitation are important. COPD and bronchiectasis are treated according to guidelines. Multidisciplinary collaboration in RA-ILD is important and treatment decisions are based on clinical experience and imaging suggesting an inflammatory or fibrotic phenotype.

Diagnostic delay in IPF impacts progression-free survival, quality of life and hospitalisation rates.

BACKGROUND: The diagnosis of idiopathic pulmonary fibrosis (IPF) is often delayed up to several years. The objective of this study was to assess the impact of the diagnostic delay on progression-free survival, quality of life and hospitalisation rates. METHODS: A total of 264 incident patients with IPF were included immediately after their diagnosis and followed for up to 5 years, with regular collection of clinical data, quality-of-life questionnaires and assessment of disease progression. Hospitalisation data were extracted from electronic patient records. Analyses were performed on the entire cohort and strata according to forced vital capacity (FVC) at diagnosis. RESULTS: A long diagnostic delay (>1 year) was associated with worse progression-free survival compared with a short diagnostic delay (<1 year) (HR: 1.70, 95% CI: 1.18 to 2.46, p=0.004) especially in patients with mild disease at the time of diagnosis (FVC>80% predicted). Mean total scores of the St. George's respiratory questionnaire (SGRQ), a derived IPF-specific version of the SGRQ and the chronic obstructive pulmonary disease assessment test (CAT) were consistently higher in patients with long diagnostic delays, indicating worse quality of life. Mean hospitalisation rates were higher during the first year after diagnosis (Incidence rate ratio [IRR]: 3.28, 95% CI: 1.35 to 8.55, p=0.01) and during the entire follow-up (IRR: 1.74, 95% CI: 1.01 to 3.02, p=0.04). CONCLUSION: A diagnostic delay of more than 1 year negatively impacts progression-free survival, quality of life and hospitalisation rates in patients with IPF. These findings highlight the importance of an early diagnosis for proper management of IPF. TRIAL REGISTRATION NUMBER: NCT02755441.

Aspergilloma complicating previous COVID-19 pneumonitis - a case report.

Aspergillomas are found in pre-existing cavities in pulmonary parenchyma. To the best of our knowledge, aspergilloma has not previously been reported in COVID-19-associated pulmonary architecture distortion combined with barotrauma from invasive mechanical ventilation therapy. We present a case of a 67-year-old woman, who suffered from severe COVID-19 in the summer of 2020 with no suspicion of infection with Aspergillus in the acute phase. Ten months after discharge from her COVID-related admission, she developed bilateral aspergillomas diagnosed by image diagnostics, bronchoscopy, and blood samples, and she now receives antifungal therapy. We would like to raise awareness on aspergilloma in post-COVID-19 patients, since it is an expected long-term complication to COVID-19 patients with pulmonary architectural distortion.

Validation of a derived version of the IPF-specific Saint George's Respiratory Questionnaire.

BACKGROUND: Health-related quality of life (HRQL) is impaired in patients with idiopathic pulmonary fibrosis (IPF). HRQL is often measured using the St. George's Respiratory Questionnaire (SGRQ) despite the development of an IPF-specific version (SGRQ-I). Using data from a real-world cohort of patients with IPF, we aimed to transform SGRQ into a derived version of SGRQ-I, SGRQ-Ider, to examine the cross-sectional and longitudinal validity of SGRQ-Ider and to compare SGRQ-Ider to SGRQ-I. METHODS: Based on results from SGRQ, SGRQ-Ider was derived applying the algorithm used to develop SGRQ-I. Of the 50 items in SGRQ, 34 items were retained in SGRQ-Ider. Response options for seven items were collapsed and minor adjustments were made to the weights of two items after correspondence with the developers of SGRQ-I. Cross-sectional validation, responsiveness and minimal clinically important difference (MCID) were assessed by comparison to other HRQL instruments, pulmonary function tests and 6-min walk test performed at baseline, 6 and 12 months. Furthermore, the association between SGRQ-Ider scores and mortality was examined. RESULTS: A total of 150 IPF patients participated and 124 completed follow-up at 12 months. SGRQ-Ider performed comparably to SGRQ-I with a high concurrent validity, good test-retest reliability and high known-groups validity. SGRQ-Ider was responsive to change in HRQL and physiological anchors. MCID of SGRQ-Ider for improvement and deterioration was 3.5 and 5.7, respectively. SGRQ-Ider scores were associated with mortality in both univariate (HR 1.82, 95% CI 1.42-2.34 per 20-point increase) and multivariate analyses (HR 1.57, 95% CI 1.20-2.05 per 20-point increase). CONCLUSIONS: The SGRQ-Ider is a valid, reliable and responsive HRQL instrument in patients with IPF and has psychometric properties comparable to SGRQ-I. Thus, SGRQ results can reliably be transformed into the SGRQ-Ider. The MCID estimates were calculated for improvement and deterioration separately. Increasing SGRQ-Ider score was associated with increased mortality.

Clusters of comorbidities in idiopathic pulmonary fibrosis.

INTRODUCTION: Comorbidities are common in patients with idiopathic pulmonary fibrosis (IPF) and negatively impact health-related quality of life, health-care costs and mortality. Retrospective studies have focused on individual comorbidities, but clusters of multiple comorbidities have rarely been analysed. This study aimed to comprehensively and prospectively assess comorbidities in a multicentre, real-world cohort of patients with IPF, including prespecified conditions of special interest and to analyse clusters of comorbidities and examine characteristics, disease course and mortality of the clusters. METHODS: Several measurements, questionnaires, medications and medical history were combined to assess comorbidities. Using self-organizing maps, clusters of comorbidities were identified and phenotypes characterized. Disease course was assessed using mixed effects models and mortality using Cox regression. RESULTS: One-hundred and fifty IPF patients were included prospectively. All except one patient suffered from at least one comorbidity and multimorbidity was common. Arterial hypertension, gastro-oesophageal reflux disease, hypercholesterolemia, emphysema and obstructive sleep apnea were most prevalent. Four comorbidity clusters were identified. Each cluster had distinct comorbidity profiles, patient characteristics, symptom burden and disease severity. Patients with fewer comorbidities had better exercise capacity and less dyspnea at baseline, but a trend towards faster deterioration was observed. Mortality analyses showed no significant differences between clusters. CONCLUSIONS: Multimorbidity is prevalent in patients with IPF. Four specific clusters of comorbidities may represent phenotypes in IPF. A trend towards faster decline in exercise capacity and dyspnea was observed in patients with fewer comorbidities. Increased knowledge of comorbidities facilitates prevention and treatment of comorbidities in patients with IPF.

Methotrexate and risk of interstitial lung disease and respiratory failure in rheumatoid arthritis: a nationwide population-based study.

OBJECTIVES: MTX is the most commonly recommended DMARD for first-line treatment of RA, however, it has been hypothesized to cause lung disease as an adverse effect. We investigated the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in persons with RA treated with MTX and other medications. METHODS: From the Danish National Patient Register (NPR) and the DANBIO register for rheumatic diseases, we retrieved data on 30 512 persons with RA registered in 1997-2015. Information on ILD and respiratory failure was obtained from the NPR. Information on age and sex for all Danish citizens was obtained from the Danish Civil Registration System. MTX and other medication purchases were retrieved from the Danish Prescription Registry. Associations between MTX and lung disease outcomes were analysed in Cox regression models with adjustment for age, calendar time, sex and other medications. Standardized incidence ratios (SIRs) of lung disease were calculated to compare the RA population with the general population. RESULTS: There was no increased risk of lung disease with MTX treatment [one or more purchases compared with no purchases; HR 1.00 (95% CI 0.78, 1.27) for ILD and 0.54 (95% CI 0.43, 0.67) for respiratory failure] at the 5 year follow-up. The SIR was three to four times higher for ILD in MTX-treated persons with RA, but similar to the whole RA population compared with the background population. CONCLUSION: Persons with RA had an increased risk of ILD compared with the general population, but there was no further increased risk associated with MTX treatment.

Proactive prophylaxis with azithromycin and hydroxychloroquine in hospitalized patients with COVID-19 (ProPAC-COVID): a statistical analysis plan.

BACKGROUND: There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease. METHODS: The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis. DISCUSSION: This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. TRIAL REGISTRATION: ClinicalTrials.gov NCT04322396 . Registered on 26 March 2020.

Responsiveness and minimal clinically important difference of SGRQ-I and K-BILD in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) specific version of St. George's Respiratory Questionnaire (SGRQ-I) and King's Brief Interstitial Lung Disease questionnaire (K-BILD) are validated health-related quality of life (HRQL) instruments, but no or limited data exist on their responsiveness and minimal clinically important difference (MCID). The objectives of this study were to assess responsiveness of SGRQ-I and K-BILD and determine MCID separately for deterioration and improvement in a large, prospective cohort of patients with IPF in a real-world setting. METHODS: Consecutive patients with IPF were recruited. SGRQ-I, K-BILD, SGRQ, Shortness of Breath Questionnaire, pulmonary function tests and 6-min walk test measurements were obtained at baseline and at six and 12 months; at six and 12 months, patients also completed Global Rating of Change Scales. Responsiveness was assessed using correlation coefficients and linear regression. Cox regression was used for mortality analyses. MCID was estimated using receiver operating characteristic curves with separate analyses for improvement and deterioration. RESULTS: A total of 150 IPF patients were included and 124 completed the 12-month follow-up. Based on all HRQL anchors and most physiological anchors, responsiveness analyses supported the evidence pointing towards SGRQ-I and K-BILD as responsive instruments. Multivariate analyses showed an association between SGRQ-I and mortality (HR: 1.18, 95% CI: 1.02 to 1.36, p = 0.03) and a trend was found for K-BILD (HR: 0.82, 95% CI: 0.64 to 1.05, p = 0.12). MCID was estimated for all domains of SGRQ-I and K-BILD. MCID for improvement differed from deterioration for both SGRQ-I Total (3.9 and 4.9) and K-BILD Total (4.7 and 2.7). CONCLUSIONS: SGRQ-I and K-BILD were responsive to change concerning both HRQL and most physiological anchors. MCID was determined separately for improvement and deterioration, resulting in different estimates; especially a smaller estimate for deterioration compared to improvement in K-BILD. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT02818712. Registered 30 June 2016.

Validation of the King's Brief Interstitial Lung Disease questionnaire in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Health-related quality of life (HRQL) is impaired in patients with idiopathic pulmonary fibrosis (IPF). The King's Brief Interstitial Lung Disease questionnaire (K-BILD) is a validated measure of HRQL, but no previous studies have focused on the validity of K-BILD in IPF. Moreover, the relationship between K-BILD and dyspnoea or the 6-min walk test (6MWT) has not been assessed. The aim of this study was to validate K-BILD in the largest cohort of patients with IPF to date and assess how K-BILD correlates to dyspnoea and 6MWT. METHODS: Firstly, K-BILD was translated into Danish using validated translation procedures. Consecutive patients with IPF were recruited. At baseline, patients completed K-BILD, the IPF-specific version of St. Georges Respiratory Questionnaire, University of California, San Diego Shortness of Breath Questionnaire (SOBQ) Short Form-36, and pulmonary function tests and 6MWT were performed. After 14 days, K-BILD and Global Rating of Change Scales were completed. Internal consistency, concurrent validity, test-retest reliability and known groups validity were assessed. Analyses were also performed in subgroups of patients with different time since diagnosis. RESULTS: At baseline, 150 patients with IPF completed the questionnaires, and 139 patients completed the questionnaires after 14 days. K-BILD had a high internal consistency (Cronbach's α = 0.92). The concurrent validity was strong compared to SOBQ (r = - 0.66) and moderate compared to 6MWT (r = 0.43). Intraclass correlation coefficients (ICC = 0.91) and a Bland Altman plot demonstrated a good reliability. K-BILD was also able to discriminate between patients with different stages of disease (p < 0.002, Δscore > 7.4) and most results were comparable in patients with different time since diagnosis. CONCLUSION: K-BILD is a valid and reliable instrument in patients with IPF and in patients with different time since diagnosis. To a major extent, K-BILD scores reflected the impact of dyspnoea on HRQL and the impact of physical functional capacity measured by the 6MWT to a moderate degree. Compared to PFTs alone, K-BILD provides additional information on the burden of living with IPF, and importantly, K-BILD is simple to implement in both research and clinical contexts. TRIAL REGISTRATION: Clinicaltrials.org (NCT02818712) on 30 June 2016.

Chest x-ray findings in tuberculosis patients identified by passive and active case finding: A retrospective study.

BACKGROUND: Chest x-ray is central in screening and diagnosis of tuberculosis. However, sputum culture remains gold standard for diagnosis. AIM: To establish the rate of normal chest x-rays in tuberculosis patients found by spot sputum culture screening, and compare them to a group identified through passive case finding. METHOD: Chest x-rays from 39 culture-positive patients, identified by spot sputum culture screening in Copenhagen from 2012 to 2014, were included in the study (spot sputum culture group(SSC)). 39 normal chest x-rays from persons screened by mobile x-ray, and 39 chest x-rays from tuberculosis-patients identified through passive case finding(PCF) were anonymised and randomised. Two respiratory physicians and two radiologists assessed the chest x-rays. RESULTS: The normal chest x-ray rate was higher in the non-tuberculosis control group (median = 32 (82.1%), range = 74.4% - 100%), compared to the SSC group (median = 7 (17.9%), range = 10.3% - 33.3%), and the PCF controls (median = 3(7.7%), range = 2.6% - 15.4%). In the SSC group 14 (35.9%) were categorized as normal by at least one study participant. CONCLUSION: A substantial minority of patients diagnosed with tuberculosis by spot sputum culture screening, and through passive case finding would not have been identified with chest x-ray alone, highlighting that a normal chest x-ray does not exclude pulmonary tuberculosis.

Validation of the IPF-specific version of St. George's Respiratory Questionnaire.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have impaired health-related quality of life (HRQL). To measure HRQL, an IPF-specific version of the St. George's Respiratory Questionnaire (SGRQ-I) was developed, but not sufficiently validated. This study aimed to assess the validity (i.a. known-groups validity and concurrent validity) and test-retest reliability of SGRQ-I in IPF patients with different disease durations. METHODS: Patients with IPF were consecutively recruited and completed SGRQ, SGRQ-I, King's Brief Interstitial Lung Disease questionnaire (K-BILD), University of California, San Diego Shortness of Breath Questionnaire (SOBQ) and Short Form-36 (SF-36) along with pulmonary function tests and a 6-min walk test (6MWT) at baseline. After two weeks, SGRQ-I and Global Rating of Change Scales (GRCS) were completed. RESULTS: At baseline and after two weeks, 150 and 134 patients completed the questionnaires, respectively. The internal consistency of SGRQ-I was high (Cronbach's α = 0.92). Good concurrent validity was demonstrated by high intraclass correlation coefficients (ICC = 0.97), Bland-Altman plots and moderate to strong correlations to K-BILD, SOBQ and SF-36 (r = - 0.46 to 0.80). High ICC (0.92) and a Bland-Altman plot indicated good test-retest reliability. SGRQ-I was good at discriminating between patients with different stages of disease (Δscore > 18.1, effect sizes > 0.10). Validity was similar across groups of different disease duration. CONCLUSIONS: SGRQ-I proved to be valid at distinguishing between different disease severities, valid compared to other HRQL instruments, applicable across different disease durations and reliable upon repetition. SGRQ-I is a valid option for measuring HRQL in patients with IPF. TRIAL REGISTRATION: The study was registered at clinicaltrials.org ( NCT02818712 ) on 15 June 2016.

Risk factors for diagnostic delay in idiopathic pulmonary fibrosis.

BACKGROUND: Surveys and retrospective studies of patients with idiopathic pulmonary fibrosis (IPF) have shown a significant diagnostic delay. However, the causes and risk factors for this delay are not known. METHODS: Dates at six time points before the IPF diagnosis (onset of symptoms, first contact to a general practitioner, first hospital contact, referral to an interstitial lung disease (ILD) centre, first visit at an ILD centre, and final diagnosis) were recorded in a multicentre cohort of 204 incident IPF patients. Based on these dates, the delay was divided into specific patient-related and healthcare-related delays. Demographic and clinical data were used to determine risk factors for a prolonged delay, using multivariate negative binomial regression analysis. RESULTS: The median diagnostic delay was 2.1 years (IQR: 0.9-5.0), mainly attributable to the patients, general practitioners and community hospitals. Male sex was a risk factor for patient delay (IRR: 3.84, 95% CI: 1.17-11.36, p = 0.006) and old age was a risk factor for healthcare delay (IRR: 1.03, 95% CI: 1.01-1.06, p = 0.004). The total delay was prolonged in previous users of inhalation therapy (IRR: 1.99, 95% CI: 1.40-2.88, p <  0.0001) but not in patients with airway obstruction. Misdiagnosis of respiratory symptoms was reported by 41% of all patients. CONCLUSION: Despite increased awareness of IPF, the diagnostic delay is still 2.1 years. Male sex, older age and treatment attempts for alternative diagnoses are risk factors for a delayed diagnosis of IPF. Efforts to reduce the diagnostic delay should focus on these risk factors. TRIAL REGISTRATION: This study was registered at http://clinicaltrials.gov (NCT02772549) on May 10, 2016.

Spousal bereavement after fibrotic interstitial lung disease: A qualitative study.

INTRODUCTION: Fibrotic interstitial lung disease (f-ILD) comprises a group of diseases with lung scarring and reduced life expectancy. The short time from diagnosis to death affects the patients' bereaved spouses, who risk developing prolonged grief. In Denmark palliative care is most often offered to cancer patients. AIM: We aimed to investigate the experience of spouses of f-ILD patients during the final stages of illness and up to the first year after the patient's death to investigate if palliative care could ease the transition and prevent PGD. METHODS: Our study had a qualitative design triangulating in-depth interviews, field notes, participant diaries and the prolonged grief questionnaire PG-13. We included 20 spouses and applied thematic analysis. Initial coding was performed deductively according to the chronological stages of before, during and after the death of the patient. We subsequently coded inductively within the stages. RESULTS: During the final days the spouses experienced emotional ambivalence shifting between hope, acceptance and despair. Factors affecting the spouses during the final hours were the timing, location, and process of death. After the patient's death the spouses experienced feelings of grief and optimism as they moved toward a new life on their own. CONCLUSIONS: Some of the factors affecting the spouses and potentially causing prolonged grief might be alleviated by offering palliative/supportive care and advance care planning to f-ILD patients and their family.

Validation of the COPD Assessment Test (CAT) in patients with idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with high morbidity and mortality. A reliable and manageable questionnaire that assesses patients' quality of life is needed to help to improve the content of clinical consultations. The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is used in clinical practice; therefore, the aim of this study was to investigate correlations among the CAT, St. George's Respiratory Questionnaire (SGRQ) and clinical parameters among patients diagnosed with IPF. Methods: A retrospective cohort design was employed in which 87 patients diagnosed with IPF who were receiving treatment at an outpatient clinic were included. Results: The CAT was found to be significantly correlated with SGRQ (p < 0.001). Furthermore, the CAT was significantly correlated with all of the included physiological variables. Conclusions: This add to support the validity of the COPD Assessment test (CAT) as a measure of symptoms in patients with IPF which in clinical practice in combination with dialogue between healthcare professionals and the patient, can help to improve the content of a clinical consultation.