Differences in Treatment Response in Bronchial Epithelial Cells from Idiopathic Pulmonary Fibrosis (IPF) Patients: A First Step towards Personalized Medicine?

Idiopathic pulmonary fibrosis (IPF) has a detrimental prognosis despite antifibrotic therapies to which individual responses vary. IPF pathology is associated with oxidative stress, inflammation and increased activation of SRC family kinases (SFK). This pilot study evaluates individual responses to pirfenidone, nintedanib and SFK inhibitor saracatinib, markers of redox homeostasis, fibrosis and inflammation, in IPF-derived human bronchial epithelial (HBE) cells. Differentiated HBE cells from patients with and without IPF were analyzed for potential alterations in redox and profibrotic genes and pro-inflammatory cytokine secretion. Additionally, the effects of pirfenidone, nintedanib and saracatinib on these markers were determined. HBE cells were differentiated into a bronchial epithelium containing ciliated epithelial, basal, goblet and club cells. NOX4 expression was increased in IPF-derived HBE cells but differed on an individual level. In patients with higher NOX4 expression, pirfenidone induced antioxidant gene expression. All drugs significantly decreased NOX4 expression. IL-6 (p = 0.09) and IL-8 secretion (p = 0.014) were increased in IPF-derived HBE cells and significantly reduced by saracatinib. Finally, saracatinib significantly decreased TGF-ß gene expression. Our results indicate that treatment responsiveness varies between IPF patients in relation to their oxidative and inflammatory status. Interestingly, saracatinib tends to be more effective in IPF than standard antifibrotic drugs.

[Linguistic Validation of the "German Lung Fibrosis Health Related Quality of Life Questionnaire"]. / Sprachliche Validierung des Fibrose-Fragebogens zur Erfassung der Lebensqualität bei Patienten mit idiopathischer Lungenfibrose und idiopathischer nichtspezifischer interstitieller Pneumonie.

Health status and quality of life are impaired in patients with idiopathic pulmonary fibrosis (IPF) and idiopathic non-specific interstitial fibrosis (iNSIP). In Germany exists only the K-BILD questionnaire for patients with ILD 1 in a professional translation by Kreuter et al. 2 This questionnaire focuses on the main problems in patients with progressive lung fibrosis in a limited manner. Therefore a new quality of life questionnaire for patients with idiopathic pulmonary fibrosis was developed and linguistically validated. METHODS: The linguistic validation of our questionnaire was carried out in a multistage process in collaboration with the developer of the questionnaire and bilingual, professional translators. Review by the developers and back translations as well as clinical assessment by IPF- and iNSIP-patients ensured that the translated questionnaire reflected the intention of the original English version of our questionnaire.Cross-validation was carried out with the St. Georges Respiratory Questionnaire (SGRQ). RESULTS: The new questionnaire concerning the health status was composed in English and German language. The questions cover five scales (sensitivity, selectivity and symptoms like breathlessness and cough and a visual analog scale on general health status) with 23 items. CONCLUSIONS: The results show that the FFB maps the special needs of the patients with IPF and iNSIP well and can support clinical and scientific questions and can be helpful in monitoring the clinical course.

Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. OBJECTIVES: The aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. METHODS: 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. RESULTS: Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores. CONCLUSIONS: Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.

Influence of built environment on quality of life changes in African-American patients with non-metastatic breast cancer.

Research links the built environment to health outcomes, but little is known about how this affects quality of life (QOL) of African American breast cancer patients, especially those residing in disadvantaged neighborhoods. Using latent trajectory models, we examined whether the built environment using Google Street View was associated with changes in QOL over a 2-year follow-up in 228 newly diagnosed African American breast cancer patients. We measured QOL using the RAND 36-Item Health Survey subscales. After adjusting for covariates, improvement in emotional well-being and pain over time was greater for women living on streets with low-quality (vs. high-quality) sidewalks.

[German Guideline for Idiopathic Pulmonary Fibrosis]. / S2K-Leitlinie zur Diagnostik der idiopathischen Lungenfibrose.

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since publication of the international IPF guideline in the year 2011 and Update 2018 several studies and technical advances occurred, which made a new assessment of the diagnostic process mandatory. In view of the antifibrotic drugs which have been approved for the treatment of IPF patients, the goal of this guideline is to foster early, confident and effective diagnosis of IPF. The guideline focusses on the typical clinical setting of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardised questionnaires, serologic testing and cellular analysis of bronchoalveolar lavage. High resolution computed tomography remains crucial in the diagnostic work-up. If it is necessary to obtain specimen for histology transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom bronchoscopic diagnosis did not provide the information needed. Despite considerable progress, IPF remains a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.

Cessation and reduction in smoking behavior: impact of creating a smoke-free home on smokers.

The aim of this study was to assess the effect of a creating a smoke-free home (SFH) on cessation and reduction of cigarette smoking on low-income smokers. This secondary data analysis uses data from study participants who were originally recruited through 2-1-1 information and referral call centers in Atlanta (Georgia, 2013), North Carolina (2014) and the Texas Gulf Coast (2015) across three randomized controlled trials testing an intervention aimed at creating SFHs, pooling data from 941 smokers. Participants who reported adopting a SFH were more likely to report quitting smoking than those who did not adopt a SFH. This was true at 3-month follow-up and even more pronounced at 6-month follow-up and persisted when considering only those who consistently reported no smoking at 3 and 6 months. Among those who did not stop smoking, the number of cigarettes per day declined significantly more and quit attempts were more frequent for those who created a SFH compared with those who did not. Findings suggest that creating a SFH facilitates cessation, reduces cigarette consumption and increases quit attempts. Future studies should assess the long-term impact of SFHs on sustaining cessation.

[DGP Interstitial Lung Disease Patient Questionnaire]. / Patientenfragebogen zur Erfassung der Ursachen interstitieller und seltener Lungenerkrankungen ­ klinische Sektion der DGP.

BACKGROUND: Interstitial lung diseases (ILD) encompass different heterogeneous, mainly chronic diseases of the pulmonary interstitium and/or alveoli with known and unknown reasons. The diagnostic of ILD is challenging and should be performed interdisciplinary. The medical history is of major importance and therefore, in German-speaking countries the Frankfurter Bogen (published in 1985) was utilised to scrutinise the medical history of the patient. This by now more than 30-years-old questionnaire requires a revision with regard to content and language. METHOD: Under the auspices of the clinical section of the DGP the new Interstitial Lung Disease Patient Questionnaire was developed in collaboration amongst pulmonologist, occupational medicine physicians and psychologists and supported by patient support groups. The questionnaire was finally optimised linguistically with the help of patients. RESULTS: The newly developed patient questionnaire for interstitial and rare lung diseases encompasses different domains: initial and current symptoms, medical history questions including prior drug treatments, previous pulmonary and extrapulmonary diseases, potential exposition at home, work and leisure time as well as family history and travelling. CONCLUSION: The newly developed questionnaire can facilitate the diagnosis in patients with suspicion on interstitial lung disease in clinical routine.

[Expert Knowledge and Supporting Advice for the Clinical Use of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis]. / Erfahrungen und unterstützende Hinweise zur Anwendung von Nintedanib bei Patienten mit idiopathischer Lungenfibrose.

In October 2016, a group of German IPF experts were invited by Boehringer Ingelheim to meet in Frankfurt with the aim, (a) to discuss relevant aspects of the management and treatment of idiopathic pulmonary fibrosis (IPF) using nintedanib; and, (b) to provide supportive advice for daily clinical practice with nintedanib. The resulting information compiled in this document is confined to practical issues regarding the use of nintedanib in patients with IPF. Where different therapeutic options were available, the choice of IPF medication was not discussed and the experts alluded to current guidelines for the diagnosis and treatment of IPF.The participants discussed a comprehensive spectrum of clinical questions related to 10 different topics, including patient-related aspects at initiation of IPF therapy, the treatment of anticoagulated IPF patients, and the handling of nintedanib-related adverse events such as gastrointestinal side effects and elevated liver enzymes. In addition, the experts evaluated therapeutic options for IPF patients with continuous disease progression, clinical scenarios that justify discontinuation of nintedanib treatment, and therapeutic options for IPF patients with an acute exacerbation or severe infection. Finally, the participants discussed the handling of nintendanib before/after elective surgical intervention (e. g. lung transplantation) and the current evidence for antifibrotic combination therapy in patients with IPF.For each topic discussed, the resulting information incorporates published evidence from clinical trials. In case of insufficient or lacking evidence, the experts have formulated recommendations based on their personal clinical experience and evaluation.

Evaluation of an online training for improving self-reported evidence-based decision-making skills in cancer control among public health professionals.

OBJECTIVES: The purpose of this evaluation was to assess the effect of the online evidence-based cancer control (EBCC) training on improving the self-reported evidence-based decision-making (EBDM) skills in cancer control among Nebraska public health professionals. STUDY DESIGN: Cross-sectional group comparison. METHODS: Previously developed EBDM measures were administered via online surveys to 201 public health professionals at baseline (comparison group) and 123 professionals who took part in the training. Respondents rated the importance of and their skill level in 18 EBCC skills. Differences were examined using analysis of variance models adjusted for gender, age, years at agency, and years in position, and stratified by respondent educational attainment. RESULTS: Among professionals without an advanced degree, training participants reported higher overall skill scores (P = .016) than the baseline non-participant group, primarily driven by differences in the partnerships and collaboration and evaluation domains. No differences in importance ratings were observed. Among professionals with advanced degrees, there were no differences in skill scores and small differences in importance scores in the expected direction (P < .05). Respondents at baseline rated the following facilitators for EBDM as important: expectations from agency leaders and community partners, high priority placed on EBDM by leadership, trainings, and positive feedback. They also reported using a variety of materials for making decisions about programs and policies, though few used individual scientific studies. CONCLUSIONS: EBCC led to improved self-reported EBDM skills among public health professionals without an advanced degree, though a gap remained between the self-reported skills and the perceived importance of the skills. Further research on training content and modalities for professionals with higher educational attainment and baseline skill scores is needed.

[German Validation of the "King's Brief Interstitial Lung Disease (K-Bild) Health Status Questionnaire"]. / Deutschsprachige Validierung des "Kingʼs Brief Interstitial Lung Disease (K-BILD)" Lebensqualitätsfragebogens für interstitielle Lungenerkrankungen.

Background: Health status and quality of life are impaired in patients with interstitial lung disease (ILD). To assess these parameters in ILD patients no valid and reliable questionnaire exists in German language so far. The K-BILD questionnaire is a brief and valid tool to evaluate health status in ILD patients, with no validated German version. Method: The linguistic validation of K-BILD was carried out in a multistage process in collaboration with the developer of the questionnaire and bilingual, professional translators. Review by the developers and back translations as well as clinical assessment by ILD patients ensured that the translated questionnaire reflected the intention of the original K-BILD. Results: A German version of K-BILD with 15 questions concerning the health status was composed. The questions cover the three domains breathlessness and activities, psychological aspects and chest symptoms. Problems in understanding or difficulties in replying to the questions were not stated by the ILD patients. Conclusion: The German version of the K-BILD questionnaire allows the clinical and scientific use to measure reliable health quality in ILD patients.

[Pulmonary manifestations in collagen vascular diseases]. / Pulmonale Manifestationen bei Kollagenosen.

CLINICAL/METHODICAL ISSUE: Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. STANDARD RADIOLOGICAL METHODS: The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. PERFORMANCE: The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. ACHIEVEMENTS: Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. PRACTICAL RECOMMENDATIONS: At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management.

[Pulmonary granulomatous diseases and pulmonary manifestations of systemic granulomatous disease : Including tuberculosis and nontuberculous mycobacteriosis]. / Pulmonale granulomatöse Erkrankungen und pulmonale Manifestationen systemischer Granulomatosen : Inklusive Tuberkulose und nichttuberkulöse Mykobakteriosen.

CLINICAL/METHODICAL ISSUE: Granulomas as signs of specific inflammation of the lungs are found in various diseases with pulmonary manifestations and represent an important imaging finding. STANDARD RADIOLOGICAL METHODS: The standard imaging modality for the work-up of granulomatous diseases of the lungs is most often thin-slice computed tomography (CT). There are a few instances, e. g. tuberculosis, sarcoidosis and silicosis, where a chest radiograph still plays an important role. METHODICAL INNOVATIONS: Further radiological modalities are usually not needed in the routine work-up of granulomatous diseases of the chest. In special cases magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT scans play an important role, e. g. detecting cardiac sarcoidosis by cardiac MRI or choline C­11 PET-CT in diagnosing lung carcinoma in scar tissue after tuberculosis. PERFORMANCE: The accuracy of thin-slice CT is very high for granulomatous diseases. ACHIEVEMENTS: In cases of chronic disease and fibrotic interstitial lung disease it is important to perform thin-slice CT in order to diagnose a specific disease pattern. Thin-slice CT is also highly sensitive in detecting disease complications and comorbidities, such as malignancies. Given these indications thin-slice CT is generally accepted in the routine daily practice. PRACTICAL RECOMMENDATIONS: A thin-slice CT and an interdisciplinary discussion are recommended in many cases with a suspected diagnosis of pulmonary granulomatous disease due to clinical or radiographic findings.