The smell of lung disease: a review of the current status of electronic nose technology.

There is a need for timely, accurate diagnosis, and personalised management in lung diseases. Exhaled breath reflects inflammatory and metabolic processes in the human body, especially in the lungs. The analysis of exhaled breath using electronic nose (eNose) technology has gained increasing attention in the past years. This technique has great potential to be used in clinical practice as a real-time non-invasive diagnostic tool, and for monitoring disease course and therapeutic effects. To date, multiple eNoses have been developed and evaluated in clinical studies across a wide spectrum of lung diseases, mainly for diagnostic purposes. Heterogeneity in study design, analysis techniques, and differences between eNose devices currently hamper generalization and comparison of study results. Moreover, many pilot studies have been performed, while validation and implementation studies are scarce. These studies are needed before implementation in clinical practice can be realised. This review summarises the technical aspects of available eNose devices and the available evidence for clinical application of eNose technology in different lung diseases. Furthermore, recommendations for future research to pave the way for clinical implementation of eNose technology are provided.

Patient expectations, experiences and satisfaction with nintedanib and pirfenidone in idiopathic pulmonary fibrosis: a quantitative study.

BACKGROUND: Two antifibrotic drugs, nintedanib and pirfenidone, are available for treatment of idiopathic pulmonary fibrosis (IPF). Although efficacy and adverse events have been well studied, little is known about patient experiences with these drugs. We aimed to systematically and quantitatively evaluate patient expectations, experiences, and satisfaction with nintedanib and pirfenidone. Furthermore, we assessed which factors were associated with overall patient satisfaction with medication. METHODS: Outpatients with IPF prospectively completed the Patient Experiences and Satisfaction with Medication (PESaM) questionnaire before start, and after three and 6 months of antifibrotic treatment, as part of a randomized eHealth trial (NCT03420235). The PESaM questionnaire consists of an expectation module, a validated generic module evaluating patient experiences and satisfaction concerning the effectiveness, side-effects, and ease of use of a medication, and a disease-specific module about IPF. Satisfaction was scored on a scale from - 5 (very dissatisfied) to + 5 (very satisfied). RESULTS: In total, 90 patients were included, of whom 43% used nintedanib and 57% pirfenidone. After 6 months, the mean overall score for satisfaction with medication was 2.1 (SD 1.9). No differences were found in experiences and satisfaction with medication, and the number and severity of side-effects between nintedanib and pirfenidone. Perceived effectiveness of medication was rated as significantly more important than side-effects and ease of use (p = 0.001). Expectations of patients regarding effectiveness were higher than experiences after 6 months. Self-reported experience with effectiveness was the main factor associated with overall medication satisfaction. CONCLUSIONS: Patient experiences and satisfaction with antifibrotic treatment were fairly positive, and similar for nintedanib and pirfenidone. Systematic evaluation of patient expectations, experiences, and satisfaction with medication could enhance shared-decision making and guide drug treatment decisions in the future. TRIAL REGISTRATION: NCT03420235 .

Inflammation and immunity in IPF pathogenesis and treatment.

Idiopathic pulmonary fibrosis (IPF) is a progressive, and ultimately fatal, chronic interstitial lung disease characterized by enhanced extracellular matrix deposition. Repetitive alveolar epithelial injury triggers the early development of fibrosis. These injuries, in combination with dysregulated wound repair and fibroblast dysfunction, lead to ongoing tissue remodelling and fibrosis seen in end-stage pulmonary fibrosis. Although the exact etiology in IPF is unknown and probably diverse, all stages of fibrosis are accompanied by innate and adaptive immune responses. The role of inflammation as an important component in IPF etiology is controversial and sometimes seen as an epiphenomenon of fibrosis. This view is partly the result of negative multicenter trials of anti-inflammatory drugs for IPF treatment. However, new insights on the role of macrophages, the loss of T-cell and B-cell tolerance leading auto-immune responses in IPF, and the interaction of immune cells with (myo)fibroblasts have led to a slow change of this opinion. Clearly, more insight is needed to integrate basic immune mechanisms into translational research and finally new IPF therapies. In this concise review, we will focus on the role of our innate and adaptive immune system in the initiation and perpetuation of IPF pathobiology. Next, we will discuss how immune responses are influenced by current anti-fibrotic treatments, such as pirfenidone and nintedanib and end with an overview of recent and upcoming therapeutic trials that target and modulate our immune system in patients with IPF.

Needs, Perceptions and Education in Sarcoidosis: A Live Interactive Survey of Patients and Partners.

OBJECTIVES: Sarcoidosis is a chronic, multisystem disease with often a major impact on quality of life. Information on unmet needs of patients and their partners is lacking. We assessed needs and perceptions of sarcoidosis patients and their partners. METHODS: During patient information meetings in 2015 and 2017 in the Erasmus University Medical Center, we interviewed patients and partners using interactive voting boxes. Patients responded anonymously to 17 questions. Answers were projected directly on the screen in the room. RESULTS: 210 patients and 132 partners participated. Sarcoidosis has a subjective significant impact on lives of both patients and partners. The vast majority of patients and partners feel regularly misunderstood because of the general unawareness of sarcoidosis. Many patients and partners experience anxiety. Three-quarters of patients would like to see more attention and support for their psychological problems. Additionally, more supportive care for partners of sarcoidosis patients is warranted. Interactive interviewing was considered educational (91%) and pleasant (84%). DISCUSSION: This study improves awareness of needs and perceptions of patients with sarcoidosis and their partners. Sarcoidosis leads to anxiety and psychological distress and impairs well-being of patients and their partners. Attention for psychological support, better disease education, and more supportive care for partners is warranted.

A home monitoring program including real-time wireless home spirometry in idiopathic pulmonary fibrosis: a pilot study on experiences and barriers.

In idiopathic pulmonary fibrosis (IPF), home monitoring experiences are limited, not yet real-time available nor implemented in daily care. We evaluated feasibility and potential barriers of a new home monitoring program with real-time wireless home spirometry in IPF. Ten patients with IPF were asked to test this home monitoring program, including daily home spirometry, for four weeks. Measurements of home and hospital spirometry showed good agreement. All patients considered real-time wireless spirometry useful and highly feasible. Both patients and researchers suggested relatively easy solutions for the identified potential barriers regarding real-time home monitoring in IPF.

Clubbing in patients with fibrotic interstitial lung diseases.

BACKGROUND: Clubbing is associated with poor prognosis and is variably present in patients with idiopathic pulmonary fibrosis (IPF), but is also seen in other fibrotic interstitial lung diseases (ILDs). Little is known about the best methodology to assess clubbing in ILDs and, hence, the prevalence and clinical utility and clinical significance of clubbing. We therefore aimed to evaluate the agreement between different clubbing assessment methods in patients with fibrotic ILDs. Additionally, we assessed the prevalence of clubbing in different fibrotic ILDs and related clubbing to disease severity and quality of life. METHODS: Consecutive outpatients with fibrotic ILDs of two tertiary referral centers were included. Clubbing was assessed with the phalangeal depth ratio, the digital index, the Schamroth sign test, and by the treating physicians and investigator. RESULTS: We included 153 patients (100 men), mean age 65 (range 33-88), mean FVC 79% (25-145%), mean TLCOc 50% (16-104%). Different methods for assessment of clubbing had poor correlation, and as a result, clubbing prevalence varied according to the method used, ranging from 7 to 42% in the total group of patients and 7-52% in IPF. The degree of clubbing did not correlate with FVC or TLCOc (p > 0.2) or with quality of life scores, but lower mean TLCOc scores were seen in patients with clubbing than in those without. CONCLUSION: Clubbing was present in 7-42% of our fibrotic ILD cohort and showed no correlation with disease severity. Although considered an important clinical feature, assessment methods for clubbing showed no to poor agreement. Further studies are therefore needed to gain more insight into measuring clubbing reliably and the possible prognostic value and evolution of clubbing.

[A woman with a persistent cough]. / Een vrouw met een hardnekkig kuchje.

A 54-year-old, Turkish, unvaccinated woman presented with chronic cough. Bronchoscopy revealed an ulcer-like abnormality in the trachea. Surprisingly, the culture showed growth of non-toxigenic Corynebacterium diphtheriae. This is a rare pathogen that usually causes only local respiratory symptoms. At control bronchoscopy after antibiotic treatment the abnormalities were no longer seen.

Extended-spectrum beta-lactamase (ESBL)-producing enterobacteria: factors associated with infection in the community setting, Auckland, New Zealand.

We aimed to document the epidemiology of extended-spectrum beta-lactamase (ESBL)-producing enterobacteria in the Auckland community and identify factors associated with infection using a case-control study design. ESBL-producing enterobacteria were isolated from 107 infected patients, for which demographic and clinical data were available for 98 cases (92%). Escherichia coli was the predominant organism (82%), with urine as the commonest source (97%). Compared with a control group infected with ESBL-negative enterobacteria, factors significantly associated with infection on univariate analysis were: living in a residential care home (RCH); recent admission to hospital 'M'; recent antibiotic use; older age (>75 years); presence of a urinary catheter; and a history of comorbid chronic obstructive pulmonary disease (COPD), cardiovascular disease, neurological disease or recurrent urinary tract infection. On multivariate analysis, residence in RCH and COPD remained significant associations. Pulsed-field gel electrophoresis typing of the ESBL-producing E. coli identified a common strain. We concluded that residence in RCH and a history of COPD are significant associations with ESBL-producing enterobacterial infection in the Auckland community. Several spatial clusters in RCHs and a common strain suggest point-source outbreaks. A substantial number of community cases did not live in an RCH nor had been recently hospitalised, suggesting the independent generation of ESBL-producing enterobacteria in the broader community.

Regulation of BAG-1 IRES-mediated translation following chemotoxic stress.

There are three major isoforms of BAG-1 in mammalian cells, termed BAG-1L (p50), BAG-1M (p46) and BAG-1S (p36) that function as pro-survival proteins and are associated with tumorigenesis and chemoresistance. Initiation of BAG-1 protein synthesis can occur by both cap-dependent and cap-independent mechanisms and it has been shown that synthesis of BAG-1S is dependent upon the presence of an internal ribosome entry segment (IRES) in the 5'-UTR of BAG-1 mRNA. We have shown previously that BAG-1 IRES-meditated initiation of translation requires two trans-acting factors poly (rC) binding protein 1 (PCBP1) and polypyrimidine tract binding protein (PTB) for function. The former protein allows BAG-1 IRES RNA to attain a structure that permits binding of the ribosome, while the latter protein appears to be involved in ribosome recruitment. Here, we show that the BAG-1 IRES maintains synthesis of BAG-1 protein following exposure of cells to the chemotoxic drug vincristine but not to cisplatin and that this is brought about, in part, by the relocalization of PTB and PCBP1 from the nucleus to the cytoplasm.

[The technical possibilities in telemonitoring of physiological parameters]. / Technische Möglichkeiten des Telemonitorings physiologischer Parameter.

For decades, telemonitoring of vital parameters has been a recurring topic among experts. Because of its lack of economical advantages it has not established itself as a standard up to now. Thanks to novel wireless communication technologies such as Bluetooth or Zigbee, the enormous technological progress in mobile communication via GSM, GPRS, as well as UMTS and various radical medical changes within disease management programs, currently very promising new potentials for telemonitoring are appearing. This article summarizes the current technological developments, discusses their advantages and drawbacks, and deduces scenarios and technical requirements for future system architectures.

[Current status of the development of wireless sensors for medical applications]. / Aktueller Stand der Entwicklung drahtloser Sensoren für medizinische Anwendungen.

Wireless near-field transmission has been a challenge for scientists developing medical sensors for a long time. Here, instruments which measure a patient's ECG, oxygen saturation, blood pressure, peak flow, weight, blood glucose etc. are to be equipped with suitable transmission technology. Application scenarios for these sensors can be found in all medical areas where cable connections are irritating for the doctor, patient and other care personnel. This problem is especially common in sport medicine, sleep medicine, emergency medicine and intensive care. Based on its beneficial properties with regard to power consumption, range, data security and network capability, the worldwide standard radio technology Bluetooth was selected to transmit measurements. Since digital data is sent to a receiving station via Bluetooth, the measurement pre-processing now takes place in the patient sensor itself, instead of being processed by the monitor. In this article, a Bluetooth ECG, Bluetooth pulse oximeter, Bluetooth peak flow meter and Bluetooth event recorder will be introduced. On the one hand, systems can be realized with these devices, which allow patients to be monitored online (ECG, pulse oximeter). These devices can also be integrated in disease management programs (peak flow meter) and can be used to monitor high-risk patients in their home environment (event recorder).

Wireless telecardiological monitoring system for the homecare area.

In following the directive "ambulant medical treatment is preferable to in hospital treatment" the home care area is becoming more and more important in western societies. In this paper a system for monitoring cardiological risk patients is presented. Special attention was paid to an automatic detection of life-threatening events and the initiation of immediate help.

Miniaturized module for the wireless transmission of measurements with Bluetooth.

The wiring of patients for obtaining medical measurements has many disadvantages. In order to limit these, a miniaturized module was developed which digitalizes analog signals and sends the signal wirelessly to the receiver using Bluetooth. Bluetooth is especially suitable for this application because distances of up to 10 m are possible with low power consumption and robust transmission with encryption. The module consists of a Bluetooth chip, which is initialized in such a way by a microcontroller that connections from other bluetooth receivers can be accepted. The signals are then transmitted to the distant end. The maximum bit rate of the 23 mm x 30 mm module is 73.5 kBit/s. At 4.7 kBit/s, the current consumption is 12 mA.

[Development of Bluetooth wireless sensors]. / Entwicklung drahtloser Sensoren auf Basis von Bluetooth.

Wireless communication could help to overcome current obstacles in medical devices and could enable medical services to offer completely new scenarios in health care. The Bluetooth technology which is the upcoming global market leader in wireless communication turned out to be perfectly suited not only for consumer market products but also in the medical environment [1]. It offers a low power, low cost connection in the medium range of 1-100 m with a bandwidth of currently 723.2 kbaud. This paper describes the development of a wireless ECG device and a Pulse Oximeter. Equipped with a Bluetooth port, the measurement devices are enabled to transmit data between the sensor and a Bluetooth-monitor. Therefore, CSR's Bluetooth protocol embedded two-processor and embedded single-processor architecture has been used.

Quality of life in patients with malignant melanoma participating in a phase I trial of an autologous tumour-derived vaccine.

Quality of life (QOL) plays an increasingly important role in the decision-making process and the ultimate acceptability of particular treatments for patients. We prospectively examined QOL in patients with advanced melanoma treated with surgery followed by heat-shock protein peptide complex 96 (HSPPC-96) vaccine, an active, patient-specific immunotherapy. QOL (the RAND 36-Item Health Survey; SF-36) and cancer-related intrusive thoughts (Impact of Event Scale; IES) were measured at the start of treatment, 3 weeks later on the final day of treatment, and at follow-up 1 month later in 30 patients with stage III or IV malignant melanoma. Mixed model analyses revealed no significant change over time in the SF-36 Physical or Mental Component Summary scores, or the IES scores. In comparisons with other populations, at the 1 month follow-up assessment, melanoma patients reported similar QOL to patients with metastatic renal cell carcinoma who received the same treatment, significantly worse QOL on the physical dimensions and similar QOL on the psychosocial and emotional dimensions compared with the general population, similar QOL to patients with type II diabetes, and significantly better QOL on all three dimensions than patients with congestive heart failure. There was also a significant negative association between IES scores at baseline and mental health scores at each time point ( < 0.002 for all). QOL remained stable during treatment with the HSPPC-96 vaccine. In addition, patients who reported high levels of cancer-related intrusive thoughts at the start of treatment reported worse mental health at the end of the treatment.

Endocrine levels at the start of treatment are associated with subsequent psychological adjustment in cancer patients with metastatic disease.

OBJECTIVE: This study examined the association between hormonal profiles at the start of cancer treatment and subsequent psychological symptomatology. METHODS: Twenty-seven patients with metastatic renal cell carcinoma and 18 patients with metastatic melanoma completed three assessments during the course of treatment: at the start of treatment (baseline), at the end of treatment (3 weeks after baseline), and at a follow-up appointment 1 month later. Cortisol, norepinephrine, and epinephrine levels were measured at baseline using 15-hour urine samples. At each assessment, patients completed the Impact of Event Scale (IES) and the Brief Symptom Inventory (BSI). RESULTS: Patients reported moderate levels of distress throughout treatment as measured by the IES and BSI. Norepinephrine levels at the start of treatment were positively associated with IES total scores at the end of treatment and at follow-up, and cortisol levels were positively associated with IES total scores at follow-up after adjusting for baseline IES and overall distress scores. Norepinephrine levels were also positively associated with depression scores at follow-up, and cortisol levels were positively associated with depression scores at the end of treatment and at follow-up after adjusting for baseline depression and overall distress scores. CONCLUSIONS: Hormonal profiles at the start of cancer treatment are associated with subsequent psychological adjustment.

A 7-item versus 31-item food frequency questionnaire for measuring fruit, juice, and vegetable intake among a predominantly African-American population.

OBJECTIVE: This study sought to determine which of 2 fruit and vegetable food frequency questionnaires (FFQs) most closely approximated intake measured by the average of four 24-hour dietary recalls. DESIGN: Participants completed either a 31-item FFQ (n = 70) or 7-item FFQ (n = 76) on 2 occasions approximately 2 weeks apart. During the interval between FFQs1 participants provided four 24-hour dietary recalls via telephone interview. SUBJECTS/SETTING: Participants were 146 persons with food preparation responsibilities in families of students in grades 3 through 5. Respondents were predominantly African-American women in Atlanta, Ga. STATISTICAL ANALYSIS: Pearson correlation coefficients of log-transformed values estimated the reliability of each FFQ and compared FFQ estimates to reference values. The intraclass correlation coefficient evaluated consistency across 24-hour recalls. RESULTS: The first FFQs overestimated intake approximately twofold. The 31-item FFQ estimates exceeded 7-item FFQ estimates by approximately 30% . Correlations with recall estimates were high for the 7-item FFQ and moderate to low for the 31-item FFQ. The second FFQ estimates were more highly correlated to reference values. From the first to the second administration, 7-item FFQ estimates dropped from 5.2 to 2.7 servings, and 31-item FFQ estimates dropped from 6.7 to 3.5 servings. Neither FFQ produced highly reliable estimates. CONCLUSIONS: Mean total fruit and vegetable consumption was closer to reference estimates for the first 7-item FFQ and the second 31-item FFQ. The 7-item FFQ correlated more highly with reference estimates than did the 31-item FFQ. Therefore, we conclude that for African-American adults, a 1-time-administered FFQ using 7 broad food categories correlates more highly with reference values than a FFQ using 31 individual fruit and vegetable items.