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.

Immunomodulatory treatment in unclassifiable interstitial lung disease: A retrospective study of treatment response.

BACKGROUND AND OBJECTIVE: The optimal management of unclassifiable Interstitial lung disease (ILD) remains a challenge. The aim of this study was to describe pulmonary function trajectories for patients treated with immunomodulatory therapy and for untreated patients. METHODS: Clinical information and treatment data were obtained retrospectively at two ILD centres. Pulmonary function data were analysed using (1) mixed effects linear regression models with and without clinical covariates and (2) propensity score matching using gender, age, physiology (GAP) stage, smoking and presence of ground glass opacities. RESULTS: Sixty-five percent of the 249 patients included received corticosteroids and/or other immunomodulators. Treated patients had lower forced vital capacity (FVC) (72% vs. 83% predicted) and diffusing capacity for carbon monoxide (DLco) (44% vs. 60% predicted). In mixed effects linear regression, the adjusted change in FVC was -0.22%, [-0.34; -0.11], and -0.15% [-0.28;-0.012] for DLco. The difference in pulmonary function decline between treated and untreated patients was insignificant, -0.082% per month, [-0.28; 0.11], p = 0.10 for FVC and -0.14% per month, [-0.36; 0.079], p = 0.15, for DLco. In propensity score matched analysis, the difference in change in FVC was 0.039% per month, p = 0.12, and for DLco, 0.0085% per month, p = 0.7. CONCLUSION: The pulmonary function trajectories for treated and untreated patients were parallel, despite treated patients having more severe disease at baseline. The persisting differences between the groups suggest no overall effect, although improvement or stabilization may be seen in some patients. Prospective studies are needed to define subsets of patients with unclassifiable interstitial lung disease and their optimal management.

Lung cancer in patients with idiopathic pulmonary fibrosis: A retrospective multicentre study in Europe.

BACKGROUND AND OBJECTIVE: There remains a paucity of large databases for patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. We aimed to create a European registry. METHODS: This was a multicentre, retrospective study across seven European countries between 1 January 2010 and 18 May 2021. RESULTS: We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence = 10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer (HR: 1.51, [95% CI: 1.22-1.86], p < 0.0001). All-cause mortality was significantly lower for patients with IPF and lung cancer with a monocyte count of either <0.60 or 0.60-<0.95 K/µl than patients with monocyte count ≥0.95 K/µl (HR [<0.60 vs. ≥0.95 K/µl]: 0.35, [95% CI: 0.17-0.72], HR [0.60-<0.95 vs. ≥0.95 K/µl]: 0.42, [95% CI: 0.21-0.82], p = 0.003). Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics (HR: 0.61, [95% CI: 0.42-0.87], p = 0.006). In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients (HR: 0.30 [95% CI: 0.11-0.86], p = 0.02). CONCLUSION: Lung cancer exerts a dramatic impact on patients with IPF. A consensus statement for the management of patients with IPF and lung cancer is sorely needed.

Clusters of comorbidities in fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is a type of interstitial lung disease (ILD) with a variable disease course and prognosis ranging from inflammatory and self-limiting to irreversible and progressive pulmonary fibrosis. Comorbidities are common in HP and may have an impact on prognosis. Due to the heterogeneity of HP presentation and progression, the identification of specific phenotypes in relationship to disease course and outcome is essential. The aim of this study was to identify clusters of comorbidities which could represent phenotypes in fibrotic HP and examine their impact on prognosis. METHODS: Patients diagnosed with fibrotic HP at a tertiary referral center for ILD were included. Comorbidities were systematically registered and clusters of comorbidities were identified using cluster analyses. Disease progression and survival was estimated for each cluster. RESULTS: The cohort comprised 211 patients with 53.6% males, mean age 63.0, baseline FVC 72.7%, DLCO 44.1%. Median follow-up time was 1.8 years (IQR 0.7-3.9). Three clusters with distinct comorbidity profiles and clinical characteristics were identified. One cluster dominated by elder male patients with predominantly cardiovascular diseases was associated with more respiratory hospitalizations and a worse prognosis. Differences in pulmonary function or exercise capacity trajectories between clusters were not observed. CONCLUSIONS: Three clusters with distinct comorbidities were identified and could represent phenotypes in fibrotic HP not previously recognized. The worst prognosis was observed in a cluster dominated by elder males with cardiovascular diseases. Increased focus on prevention and treatment of comorbidities could potentially improve the prognosis of patients with fibrotic HP.

Comorbidities in unclassifiable interstitial lung disease.

BACKGROUND: Comorbidities are common in interstitial lung diseases (ILD) and have an important association with survival, but the frequency and prognostic impact of comorbidities in unclassifiable interstitial lung disease (uILD) remains elusive. We aimed to describe the prevalence of comorbidities and assess the impact on survival in patients with uILD. Furthermore, we aimed to identify and characterize potential phenotypes based on clusters of comorbidities and examine their association with disease progression and survival. METHODS: Incident patients diagnosed with uILD were identified at two ILD referral centers in Denmark and Germany from 2003 to 2018. The diagnosis uILD was based on multidisciplinary team meetings. Clinical characteristics and comorbidities were extracted from ILD registries and patient case files. Survival analyses were performed using Cox regression analyses, disease progression was analyzed by linear mixed effects models, and clusters of comorbidities were analyzed using self-organizing maps. RESULTS: A total of 249 patients with uILD were identified. The cohort was dominated by males (60%), former (49%) or current (15%) smokers, median age was 70 years, mean FVC was 75.9% predicted, and mean DLCO was 49.9% predicted. One-year survival was 89% and three-year survival was 73%. Eighty-five percent of the patients had ≥ 1 comorbidities, 33% had ≥ 3 comorbidities and 9% had ≥ 5 comorbidities. The only comorbidity associated with excess mortality was dyslipidemia. No association between survival and number of comorbidities or the Charlson comorbidity index was observed. Three clusters with different comorbidities profiles and clinical characteristics were identified. A significant annual decline in FVC and DLCO % predicted was observed in cluster 1 and 2, but not in cluster 3. No difference in mortality was observed between the clusters. CONCLUSIONS: The comorbidity burden in uILD is lower than reported in other types of ILD and the impact of comorbidities on mortality needs further clarification. Three clusters with distinct comorbidity profiles were identified and could represent specific phenotypes. No difference in mortality was observed between clusters, but slower disease progression was observed in cluster 3. Better understanding of disease behavior and mortality will require further studies of subgroups of uILD with longer observation time.

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.

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.

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.

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.

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.

A new definition and treatment options of allergic alveolitis.

In this review, we discuss a new definition and treatment options of allergic alveolitis (AA). AA is an immune-mediated interstitial lung disease triggered by inhaled antigens, it is defined as non-fibrotic (inflammatory) and/or fibrotic, and diagnosis relies on a multidisciplinary approach using clinical, radiological and sometimes histological assessments. Treatment involves early antigen elimination and may include corticosteroids or other immunosuppressants. Prognosis varies from reversible inflammation to irreversible fibrosis. Early detection is crucial for better outcomes.

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.

COPD-Related Anxiety: A Systematic Review of Patient Perspectives.

Background: Anxiety in patients with chronic obstructive pulmonary disease (COPD) is prevalent but often unidentified and therefore not adequately managed. Clinicians find it difficult to detect anxiety symptoms and to differentiate subclinical anxiety from anxiety disorders, because of the considerable overlap between symptoms of COPD and anxiety. Purpose: We synthesized existing qualitative research on patients' experiences of COPD-related anxiety with the purpose of gaining a richer understanding and proposing a model of the construct. Methods: Searches for qualitative studies of patients' experiences of COPD-related anxiety were conducted independently by two authors in the databases of PubMed (MEDLINE), CINAHL (EBSCO), and PsycInfo (APA). English-language studies including patients diagnosed with COPD were reviewed, and data were analyzed using thematic analysis. Results: A total of 41 studies were included in the review. Four themes related to COPD-related anxiety were identified: initial events; internal maintaining factors; external maintaining factors; and behavioral maintaining factors. Based on the identified four themes, a conceptual model of COPD-related anxiety from the patient perspective was developed. Conclusion: A conceptual model of COPD-related anxiety from the patient perspective is now available, with the potential to inform future attempts at improving identification and management of COPD-related anxiety. Future research should focus on the development of a COPD-specific anxiety questionnaire containing domains that are relevant from the patient perspective.

A serologically assessed neo-epitope biomarker of cellular fibronectin degradation is related to pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) remodeling, herein ECM degradation. Fibronectin (FN) is an important component of the ECM that is produced by multiple cell types, including fibroblasts. Extra domain B (EDB) is specific for a cellular FN isoform which is found in the ECM. We sought to develop a non-invasive test to investigate whether matrix metalloproteinase 8 (MMP-8) degradation of EDB in cellular FN results in a specific protein fragment that can be assessed serologically and if levels relate to pulmonary fibrosis. METHOD: Cellular FN was cleaved in vitro by MMP-8 and a protein fragment was identified by mass spectrometry. A monoclonal antibody (mAb) was generated, targeting a neo-epitope originating from EDB in cellular FN. Utilizing this mAb, a neo-epitope specific enzyme-linked immunosorbent assay (FN-EDB) was developed and technically validated. Serum FN-EDB was assessed in an IPF cohort (n = 98), registered at clinicaltrials.gov (NCT02818712), and in healthy controls (n = 35). RESULTS: The FN-EDB assay had high specificity for the MMP-8 degraded neo-epitope and was technically robust. FN-EDB serum levels were not influenced by age, sex, ethnicity, or BMI. Moreover, FN-EDB serum levels were significantly higher in IPF patients (median 31.38 [IQR 25.79-46.84] ng/mL) as compared to healthy controls (median 28.05 [IQR 21.58-33.88] ng/mL, p = 0.023). CONCLUSION: We developed the neo-epitope specific FN-EDB assay, a competitive ELISA, as a tool for serological assessment of MMP-8 mediated degradation of EDB in cellular FN. This study indicates that degradation of EDB in cellular FN is elevated in IPF and warrants further investigation.

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.

Current best clinical practices for monitoring of interstitial lung disease.

INTRODUCTION: Interstitial lung diseases (ILDs) are a heterogeneous group of inflammatory and/or fibrotic conditions with variable outcome and often a dismal prognosis. Since many ILDs are progressive in nature, monitoring of signs and symptoms of progression is essential to inform treatment decisions and patient counseling. Monitoring of ILDs is a multimodality process and includes all aspects of the disease, e.g. measurement of pulmonary function and exercise capacity, symptom registration and quality of life (QoL), imaging, comorbidities and/or involvement of other organs to assess disease activity, symptom burden, treatment effects, adverse events, the need for supportive and palliative care, and lung transplantation. AREAS COVERED: For this narrative review, we searched the PUBMED database to identify articles relevant for monitoring ILDs, including pulmonary function tests, exercise capacity, imaging, telemedicine, symptoms, and QoL. EXPERT OPINION: Due to the high heterogeneity of the ILDs and their disease course, an individualized multimodality approach must be applied. Future strategies include use of telemedicine for home monitoring of lung function and symptoms, use of artificial intelligence to support automatized guidance of patients, computerized evaluation of ILD changes on imaging, and new imaging tools with less radiation dosage.

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.

[Antifibrotic therapy in other fibrotic interstitial lung diseases than idiopathic pulmonary fibrosis].

Numerous studies have shown that perioperative heparin bridging in patients treated with a vitamin K antagonist leads to an increased incidence of bleeding and so far, there is no evidence that it leads to a significant reduction in postoperative thromboembolism as summarised in this review. Prophylactic dosage of heparin is recommended after major surgery. Heparin bridging is not relevant in patients receiving a direct oral anticoagulant due to the rapid onset and offset of action of DOACs.

Attitude and Barriers in Palliative Care and Advance Care Planning in Nonmalignant Chronic Lung Disease: Results From a Danish National Survey.

INTRODUCTION: Patients with chronic obstructive pulmonary disease and interstitial lung disease have a significant burden of symptoms. Many are not offered palliative care (PC). Our aim was to investigate the attitudes to and barriers for PC among physicians. METHOD: A web-based survey was conducted among members of the Danish Respiratory Society. The questionnaire included contextual (gender, age, clinical experience, type of center, patient caseload) and outcome questions (knowledge and use of statements for PC and advance care planning [ACP], practice of communication about end-of-life decisions, practice for referral to PC, barriers regarding structural surroundings, clinical skills, and organization). RESULTS: One hundred fifty-six (45%) physicians responded. Median age was 40 - 49 years and 55% were female. Fifty-two percent were specialists; 71% worked at a university hospital. The majority of physicians (60%) reported barriers for discussions about PC and ACP; 63% reported lack of time, 52% lack of multidisciplinary staff settings, 63% reported the unpredictability of the prognosis, and 20% insufficient awareness of patient's culture, religion, or spirituality. Fewer specialists than nonspecialists reported barriers toward ACP. The majority had knowledge of guidelines in PC and ACP, but only a minority used these in daily clinical practice. CONCLUSION: The attitude toward PC and ACP conversations was positive and implementation was regarded as important, but only a minority performed these conversations in practice. Main barriers were lack of time and staff. Palliative care guidelines were known but only scarcely used. Structural changes at the organizational level to improve access to palliation for patients with nonmalignant chronic lung diseases are needed.

Fatigue in idiopathic pulmonary fibrosis measured by the Fatigue Assessment Scale during antifibrotic treatment.

Background: Fatigue is a common complaint in patients with idiopathic pulmonary fibrosis (IPF) and has been reported in a considerable percentage of patients. Fatigue is also a registered side effect of pirfenidone, one of two approved antifibrotic drugs. The Fatigue Assessment Scale (FAS) was developed for assessment of fatigue in sarcoidosis and validated in patients with sarcoidosis. FAS has been used in a few IPF studies but has not been validated. Aims: To study the change in FAS after initiation of pirfenidone or nintedanib in the treatment of patients with IPF during a six-month period. Methods: Between April 2017 and January 2018, all incident patients with IPF starting antifibrotic treatment were invited to complete FAS before, four weeks, three, and six months after initiation of antifibrotic treatment. Baseline characteristics including lung function were registered. Results: Fifty-two patients were included, mean FVC% 84.8, mean DLCO% 51.4. Nintedanib was started in 25 patients; 27 patients started pirfenidone. Sixty-four percent of patients had a FAS score >22 indicating substantial fatigue at baseline. There was no statistically significant difference in FAS score for patients treated with nintedanib or pirfenidone at any time point. FAS score increased statistically significantly during the six-month follow-up. This change was driven by patients without substantial fatigue at baseline with an increase in FAS score of 8.4 points; patients with substantial fatigue at baseline experienced no statistically significant change. Conclusion: A majority of patients with IPF suffered from substantial fatigue at the time of diagnosis. Fatigue progressed over time and increasing fatigue was associated with younger age, nintedanib treatment and low degree of fatigue at baseline. There was no significant difference in FAS score between the two antifibrotic treatments at any time point, even though fatigue is not a registered side effect in nintedanib.