A Meta-analysis of Diagnostic Test Agreement Between Eucapnic Voluntary Hyperventilation and Cardiopulmonary Exercise Tests for Exercise-Induced Bronchoconstriction Abstract Introduction Exercise-induced bronchoconstriction (EIB) is very common in athletes. Cardiopulmonary exercise tests (CPET) have traditionally been used for the diagnosis of EIB. However, alternative indirect bronchoprovocation tests have recently been used as surrogate tests. One of these is the eucapnic voluntary hyperventilation (EVH). This meta-analysis studied the agreement between the two tests. Methods An extensive search in PubMed and Medline was conducted for studies where participants underwent both CPET and EVH with measurement of forced expiratory volume in 1-second (FEV1). After extracting data using two-by-two contingency tables, pooled positive and negative agreements were first calculated between the two tests, with EVH benchmarked against CPET, and then, pooled positive and negative agreements were calculated with CPET benchmarked against EVH. Results The pooled positive and negative agreements between EVH and CPET (with CPET as the reference) were 0.62 [(95% confidence interval 0.54–0.70), I2 77%] and 0.61 [(0.56–0.65)), I2 81%]. The pooled positive and negative agreements between CPET and EVH (with EVH as the reference) were 0.36 [(0.30–0.42), I2 93%] and 0.82 [(0.77–0.86), I2 78%]. The average of positive test results with EVH across all studies was greater than that of CPETs (58.84% vs. 39.51%). Conclusions Results of this meta-analysis show poor positive agreement between the two tests but high negative agreement (specifically using EVH as reference), suggesting that either test can be used for correctly identifying those without EIB. Results also suggest that the chances of a test resulting positive are higher with EVH than with CPET.

Mass Spectrometry Analysis of the Exhaled Breath Condensate and Proposal of Dermcidin and S100A9 as Possible Markers for Lung Cancer Prognosis Abstract Introduction New sampling techniques to analyse lung diseases, such as exhaled breath condensate (EBC), are a breakthrough in research field since they are less invasive and less traumatic for the patients compared to lung biopsies. Nevertheless, there is an increasing need to optimize not only the sampling protocols but the storage and processing of specimens to get accurate results. Methods Exhaled breath condensate was sampled employing the ECoScreen device. Concentrated protein was obtained after ultracentrifugation, lyophilization and reversed-phase chromatography. MALDI-time of flight (TOF)/TOF mass spectrometry (MS) was applied to determine the protein profile in EBC. Commercially available ELISA kits were used to detect the selected biomarker in the EBC after MALDI-MS proteins identification. Results The obtained EBC volume after two periods of 10 min doubled the amount obtained after 20 min. One hundred peptides were detected by MALDI-MS, and 18 proteins were identified after reversed-phase chromatography concentration. Dermcidin (P81605), S100A9 (P06702) and Cathepsin G (P08311) were selected to be analysed by ELISA. Dermcidin and S100A9 expression were statistically higher in lung cancer versus healthy volunteers. VEGF concentrations decreased, respectively, by 5.94 and 11.42-fold after 1 and 2 years of frozen EBC preservation in parallel with the declined number of proteins identified by MALDI-MS. Conclusion Exhaled breath condensate analysis combined with MS technique may become a valuable method for lung cancer screening and Dermcidin and S100A9 may serve as biomarkers for lung cancer diagnosis or prognosis.

Bronchial Thermoplasty Including the Middle Lobe Bronchus Significantly Improves Lung Function and Quality of Life in Patients Suffering from Severe Asthma Abstract Purpose Bronchial Thermoplasty (BT) is indicated in patients suffering from severe and symptomatic bronchial asthma despite maximal medical therapy. However, treatment of the right middle lobe (RML) bronchus is currently not recommended. The aim of this study was to investigate the safety and efficacy of BT if the RML bronchus is included. Methods BT was performed in 17 consecutive patients, quality of life and pulmonary function were characterized before and 90 days after BT completion. Furthermore, we performed a clean-up bronchoscopy following every BT. This study was approved by the IRB of the University of Essen (No. 17-7356 BO) and registered as a retrospective observational study at the German Clinical Trials Registry (No. DRKS 00011550). Results The median baseline values of FEV1 and Asthma Questionnaire of Life Quality (AQLQ) were 1.33 l (0.91; 1.73) and 3.01 (2.76; 3.61), respectively, and significantly improved 90 days after treatment with FEV 1 at 1.75 l (p-value 0.002) and AQLQ 3.8 (p-value < 0.05). Also the amount of oral corticosteroid necessity decreased significantly. No severe adverse events occurred due to the procedure. Clean-up bronchoscopies—when performed—revealed significant fibrinous exudation after every BT procedure. Conclusion BT including the RML bronchus is feasible. Functionally limited patients with severe asthma could potentially profit. Due to the relevant fibrinous exudation, BT should be followed by clean-up bronchoscopy, not only after RML treatment.

Lung Function Changes are More Common in Marfan Patients Who Need Major Thoracic Surgery Abstract Introduction Marfan syndrome is a genetic disorder affecting the connective tissue. Changes in lung tissue might influence respiratory function; however, a detailed respiratory functional assessment according to the need for major thoracic surgery is missing. Methods Comprehensive pulmonary examinations were performed in 55 Marfan patients including respiratory symptoms, lung function (LF) testing using European Coal and Steel Community (ECSC) reference values, TLCO and quality of life measurements. Groups included patients who did not need surgery (Mf, n = 32) and those who underwent major thoracic surgery (Mfop, n = 23). Results Respiratory symptoms affected 20% of patients. Scoliosis was significantly more frequent in the Mfop group. LF demonstrated in all Marfan patients a tendency towards airway obstruction (FEV1/FVC = 0.77 ± 0.10), more prominent in Mfop patients (0.74 ± 0.08 vs. Mf: 0.80 ± 0.11; p = 0.03). Correction of LF values using a standing height modification by arm span (Hcorrected) revealed additional changes in FVC and FEV1. TLCO and quality of life did not differ between groups. Conclusions Marfan syndrome is associated with airway obstruction, especially in patients who have undergone major thoracic surgery, indicative of more severe connective tissue malfunction. The use of arm span for height correction is suitable to evaluate LF changes in this special patient group including patients with significant scoliosis.

How the Frequency and Phenotype of Sarcoidosis is Driven by Environmental Determinants Abstract Background Sarcoidosis is a systemic disease in which the personal environment seems to drive a differentiated disease frequency and clinical expression. The main epidemiological studies suggest a key influence of potential environmentally linked exposures related to the type of occupation, the household, life style, socioeconomic status, and region of residence. Objective To provide an update on how sarcoidosis may be modulated by environmental factors. Data Sources We searched PubMed for epidemiological studies. Synthesis The risk of sarcoidosis is enhanced in people working in jobs related to agriculture, water, construction, metal machining, education, and health, and reduced in those working in jobs mainly centered on personal care. Studies have confirmed seasonal-related peaks of sarcoidosis incidence that follow geographical North–South and West–East gradients. Other personal factors include smoking, personal household exposures, and leisure activities. The evidence pointing to the crucial role of the environment in the etiopathogenesis of sarcoidosis is mounting rapidly. Few diseases so strongly combine geography, environment, gender, and ethnicity as key etiopathogenic factors, with susceptibility to any putative agent being modulated by the individual exposome and genome. Conclusion Geoepidemiological research should focus on evaluating the combined effects of environmental and genetic factors, the identification of clusters of geographically driven exposures, and more precise measurement of all personal exposures (degree of combination, length, and level of exposure).

Hepatic Hydrothorax: An Updated Review on a Challenging Disease Abstract Hepatic hydrothorax is a challenging complication of cirrhosis related to portal hypertension with an incidence of 5–11% and occurs most commonly in patients with decompensated disease. Diagnosis is made through thoracentesis after excluding other causes of transudative effusions. It presents with dyspnea on exertion and it is most commonly right sided. Pathophysiology is mainly related to the direct passage of fluid from the peritoneal cavity through diaphragmatic defects. In this updated literature review, we summarize the diagnosis, clinical presentation, epidemiology and pathophysiology of hepatic hydrothorax, then we discuss a common complication of hepatic hydrothorax, spontaneous bacterial pleuritis, and how to diagnose and treat this condition. Finally, we elaborate all treatment options including chest tube drainage, pleurodesis, surgical intervention, Transjugular Intrahepatic Portosystemic Shunt and the most recent evidence on indwelling pleural catheters, discussing the available data and concluding with management recommendations.

Sarcoidosis and Work Participation: The Need to Develop a Disease-Specific Core Set for Assessment of Work Ability Abstract Objective Sarcoidosis, an inflammatory multi-organ disease with a wide variety of clinical manifestations, affecting people of working age. Patients suffer from a broad spectrum of physical symptoms of varying severity that impact function including cognitive impairment and disabling fatigue. The Dutch Sarcoidosis Society identified a knowledge gap in various facets related to work ability. The aim of this study was to assess sarcoidosis patients’ perceived problems related to work performance, employer, and disability evaluations. Methods A cross-sectional web-based anonymous survey was conducted among Dutch sarcoidosis patients recruited through sarcoidosis patient societies and outpatient sarcoidosis clinics. This investigation queried work performance, employer support, and disability evaluations. Results The study sample included 755 patients of whom 43% (n = 328) had undergone disability evaluation and were significantly more likely to experience extrapulmonary symptoms, severe fatigue, reduced exercise capacity along with memory problems and concentration problems with higher mean FAS and SFNSL-scores. Of these 328, 37% (n = 121) perceived they had not been listened to or taken seriously at assessments, and 38% (n = 124) disagreed with the outcome of disability assessments by benefits authorities; 75% (n = 93) appealed or requested re-assessment. Discussion A better understanding of sarcoidosis-related impact on work ability and quantification of disease burden is needed. Education for medical examiners and employers on sarcoidosis may improve quality of assessments and work accommodations. Development of guidelines for benefit authorities, which consider the broad impact of sarcoidosis beyond that of reduced pulmonary function, including extra-pulmonary assessment like fatigue, cognitive difficulties, as well as other organ involvement are needed.

Counting Steps: A New Way to Monitor Patients with Pulmonary Arterial Hypertension Abstract Rationale Activity levels in patients with pulmonary arterial hypertension (PAH) have correlated with surrogate markers of disease severity. It is not known whether physical activity measures are useful in monitoring patients with PAH. Objectives This pilot study aimed to evaluate whether change in physical activity measured by an accelerometer correlates with changes in six-minute walk distance (6MWD), echocardiographic parameters, NT-proBNP, or health-related quality-of-life measures (HRQOL). Methods The study design was a prospective, observational study in subjects with prevalent PAH. Subjects wore a wrist-worn accelerometer (Fitbit Charge HR®) between two outpatient visits. Daily step count and activity levels were recorded, and the change over time was correlated with changes in 6MWD, echocardiographic parameters, HRQOL, and NT-proBNP. Measurements and Main Results 30 subjects were enrolled, of which 20 patients had adequate accelerometer data to be analyzed over the study duration. The mean duration of follow-up was 136.4 ( ± 47.3) days. The change in daily step count correlated with a change in 6MWD (r 0.43, p 0.05). Changes in duration spent in moderately active (r 0.52, p 0.02), lightly active (r 0.48, p 0.05), and sedentary activity levels (r − 0.54, p 0.02) correlated with a change in HRQOL. Changes in activity levels did not correlate with echocardiographic measures or NT-pro BNP. Conclusions Changes in daily step count and time spent at fairly active, lightly active, and sedentary activity levels correlate with changes in 6MWD, and HRQOL in subjects with PAH suggesting that accelerometry may be a useful monitoring tool.

Association of Obesity with Quantitative Chest CT Measured Airway Wall Thickness in WTC Workers with Lower Airway Disease Abstract Background We previously reported that wall area percent (WAP), a quantitative CT (QCT) indicator of airway wall thickness and, presumably, inflammation, is associated with adverse longitudinal expiratory flow trajectories in WTC workers, but that obesity and weight gain also seemed to be independently predictive of the latter. Previous studies have reported no association between WAP and obesity, so we investigated that association in nonsmoking WTC-exposed individuals and healthy unexposed controls. Methods We assessed WAP using the Chest Imaging Platform QCT system in a segmental bronchus in 118 former WTC workers, and 89 COPDGene® WTC-unexposed and asymptomatic subjects. We used multiple regression to model WAP vs. body mass index (BMI) in the two groups, adjusting for important subject and CT image characteristics. Results Unadjusted analyses revealed significant differences between the two groups with regards to WAP, age, gender, scan pixel spacing and slice interval, but not BMI or total lung capacity. In adjusted analysis, there was a significant interaction between BMI and WTC exposure on WAP. BMI was significantly and positively associated with WAP in the WTC group, but not in the COPDGene® group, but stratified analyses revealed that the effect was significant in WTC subjects with clinical evidence of lower airway disease (LAD). Discussion Unlike non-diseased subjects, BMI was significantly associated with WAP in WTC workers and, in stratified analyses, the association was significant only among those with LAD. Our findings suggest that this adverse effect of obesity on airway structure and inflammation may be confined to already diseased individuals.

C-Reactive Protein Levels and the Risk of Incident Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea Abstract Purpose Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease (CVD) but it is unclear who are at greatest risk. We determined whether the inflammatory marker, C-reactive protein (CRP), could be a useful prognostic biomarker. Methods Adult patients referred for polysomnography (PSG) with OSA were studied. Serum CRP levels were measured using ELISA the morning after PSG. Validated CV events within 4 years of PSG were ascertained by linking to provincial research datasets. Results 155 patients with OSA (AHI ≥ 5/h) had CRP measured. Median age was 53 and median AHI was 21/h. 10 patients (7.1%) suffered at least one event, but rates varied substantially by CRP (0/35 patients in the lowest quartile, and 7/39 in the highest CRP quartile). In the unadjusted analysis, patients in the highest CRP quartile (≥ 2.38 mg/L) were significantly more likely to suffer an event (odds ratio = 9.72 (95% CI 2.43–38.84), p = 0.001). CRP continued to be a significant predictor after controlling for multiple confounders. OSA severity and desaturation were not significantly associated with prospective events. Conclusions In this small preliminary study, OSA patients with an elevated CRP were significantly more likely to suffer a CVD event in the 4 years after PSG. Although these findings need to be confirmed in larger prospective cohorts, CRP may be useful in risk stratifying OSA patients to guide therapy or to identify patients that might be most appropriate for clinical trials of CVD prevention.