Effects of flexible scheduling and virtual visits on burnout for clinicians.

OBJECTIVE: Burnout is a healthcare quality problem, linked to negative impacts in patient care and healthcare providers. The pandemic prompted clinicians to adapt virtual practices and adopt more flexible, autonomous schedules. However, the impact of flexible scheduling and autonomy on provider burnout is unknown. The study aim was to evaluate the effect of flexible schedules versus standard schedules, and the amount of digital care, on burnout. METHODS: This was a prospective survey study at two time points 6 months apart. Providers from Rheumatology, Neurology, and Pediatrics completed surveys at baseline, between 6/22/2020-9/8/2020, and six months later, between 12/20/20-3/12/21. The primary outcome was the Mini-Z work life survey which measured burnout in 2 different groups: flexible schedules (FS) and standard schedules (SS) during the height of the pandemic. RESULTS: The study included 149 providers, 47 with FS and 102 with SS, who completed the survey at baseline and 6 months later. At baseline providers reported high job satisfaction (85.9%) and low burnout (29.7%), which remained consistent at 6 months. Compared to those with SS, clinicians with FS participated in a greater number of telemedicine activities at baseline, but did not differ significantly in degree of burnout (25.5% FS, 31.7% SS, p=0.45). Participants in the FS group were significantly more likely to indicate improvement in control over workload and experience reduced work-related stress compared to those in the SS group. There was no association between amount of telemedicine visits and burnout. Predictors of burnout at 6 months included Rheumatology providers and those in the 20-39 year old age group. DISCUSSION: Schedule flexibility does not appear to influence overall burnout; however it does impact variables associated with burnout such as control over workload and perceived job stress. CONCLUSIONS: Participants reported overall job satisfaction, and FS did not impact overall burnout. FS was more likely to indicate improvement in control over workload and experienced reduced work-related stress compared to SS. In addition, burnout was more likely in the 20-39 year old age group, suggesting that special focus should be paid to this age group.

Metabolomic analysis of breath volatile organic compounds reveals unique breathprints in children with inflammatory bowel disease: a pilot study.

BACKGROUND: Breath testing is becoming an important diagnostic method to evaluate many disease states. In the light of rising healthcare costs, is important to develop a simple non-invasive tool to potentially identify paediatric patients who need endoscopy for suspected inflammatory bowel disease (IBD). AIM: To analyse exhaled volatile organic compounds (VOCs) and investigate the presence of a unique breath patterns to differentiate paediatric patients with (IBD) from healthy controls. METHODS: A cross-sectional, single-centre study included paediatric IBD patients and healthy controls (age range, 5-21 years). The diagnosis of IBD was confirmed by endoscopic, histological and radiographic data. Exhaled breath was collected and analysed using a selective ion flow tube mass spectroscopy (SIFT-MS) to identify new markers or patterns of IBD. RESULTS: One hundred and seventeen patients (62 with IBD and 55 healthy controls) were included in the study. Linear discriminant analysis and principle component analysis of mass scanning ion peak data demonstrated 21 pre-selected VOCs correctly classify patients with IBD or as healthy controls; P < 0.0001. Multivariable logistic regression analysis further showed three specific VOCs (1-octene, 1-decene, (E)-2-nonene) had excellent accuracy for predicting the presence of IBD with an area under the curve (AUC) of 0.96 (95% CI: 0.93-0.99). No significant difference in VOCs was found between patients with Crohn's disease or ulcerative colitis, and no significant correlation was seen with disease activity. CONCLUSION: These pilot data support the hypothesis that a unique breathprint potentially exists for paediatric IBD in the exhaled metabolome.

Impact of switching from epoprostenol to IV treprostinil on treatment satisfaction and quality of life in patients with pulmonary hypertension.

BACKGROUND: Transition from intravenous (IV) epoprostenol to IV treprostinil in patients with pulmonary hypertension (PH) has traditionally been performed by gradually decreasing the epoprostenol dose while increasing the treprostinil dose. Preliminary data suggest that this transition can be performed more rapidly without the need for epoprostenol weaning. We conducted a single center, prospective clinical trial to assess the safety, efficacy, and treatment satisfaction of rapidly switching from epoprostenol to IV treprostinil. METHODS: This study included patients with PH who had rapidly transitioned from epoprostenol to IV treprostinil. Data collected included clinical status, adverse events, PH symptoms, and previously validated measures of quality of life and treatment satisfaction. RESULTS: Ten patients were enrolled in this study. Exercise capacity measured by mean 6-min walk distance was maintained from baseline throughout follow-up. Severity of disease as assessed by WHO functional class was maintained or improved for the majority of patients. Adverse events were minimal during the transition, and all patients remained on IV treprostinil throughout the follow-up period. A favorable impact on quality of life and treatment satisfaction measures was observed by eight weeks following the transition from epoprostenol to IV treprostinil. Specifically, time spent on drug preparation activities decreased by 39.5% with treprostinil compared to epoprostenol. CONCLUSIONS: Rapidly switching from epoprostenol to IV treprostinil can be achieved without safety concerns, with minimal patient monitoring and without the need for extended hospitalization, while favorably impacting on patients' quality of life.

Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial hypertension.

Circulating cardiac troponins are markers of myocardial injury. We sought to determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is associated with disease severity and prognosis in pulmonary arterial hypertension (PAH). cTnI was measured in 68 patients with PAH diagnostic category 1 in a research-based sensitive immunoanalyser with a lower limit of detection of 0.008 ng · mL(-1). The associations between cTnI and PAH severity and clinical outcomes were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan-Meier analysis and Cox regression models. cTnI was detected in 25% of patients. Patients with detectable cTnI had more advanced functional class symptoms, a shorter 6-min walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels. 36-month transplant-free survival was 44% in patients with detectable cTnI versus 85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold increased risk of death related to right ventricular failure or transplant (hazard ratio 4.74, 95% CI 1.89-11.89; p<0.001), even when adjusted individually for known parameters of PAH severity. Elevated plasma cTnI, even at subclinically detectable levels, is associated with more severe disease and worse outcomes in patients with PAH.

Smart sensor systems for human health breath monitoring applications.

Breath analysis techniques offer a potential revolution in health care diagnostics, especially if these techniques can be brought into standard use in the clinic and at home. The advent of microsensors combined with smart sensor system technology enables a new generation of sensor systems with significantly enhanced capabilities and minimal size, weight and power consumption. This paper discusses the microsensor/smart sensor system approach and provides a summary of efforts to migrate this technology into human health breath monitoring applications. First, the basic capability of this approach to measure exhaled breath associated with exercise physiology is demonstrated. Building from this foundation, the development of a system for a portable asthma home health care system is described. A solid-state nitric oxide (NO) sensor for asthma monitoring has been identified, and efforts are underway to miniaturize this NO sensor technology and integrate it into a smart sensor system. It is concluded that base platform microsensor technology combined with smart sensor systems can address the needs of a range of breath monitoring applications and enable new capabilities for healthcare.

Effect of the influenza A (H1N1) live attenuated intranasal vaccine on nitric oxide (FE(NO)) and other volatiles in exhaled breath.

For the 2009 influenza A (H1N1) pandemic, vaccination and infection control were the main modes of prevention. A live attenuated H1N1 vaccine mimics natural infection and works by evoking a host immune response, but currently there are no easy methods to measure such a response. To determine if an immune response could be measured in exhaled breath, exhaled nitric oxide (FE(NO)) and other exhaled breath volatiles using selected ion flow tube mass spectrometry (SIFT-MS) were measured before and daily for seven days after administering the H1N1 2009 monovalent live intranasal vaccine (FluMist®, MedImmune LLC) in nine healthy healthcare workers (age 35 ± 7 years; five females). On day 3 after H1N1 FluMist® administration there were increases in FE(NO) (MEAN±SEM: day 0 15 ± 3 ppb, day 3 19 ± 3 ppb; p < 0.001) and breath isoprene (MEAN±SEM: day 0 59 ± 15 ppb, day 3 99 ± 17 ppb; p = 0.02). MS analysis identified the greatest number of changes in exhaled breath on day 3 with 137 product ion masses that changed from baseline. The exhaled breath changes on day 3 after H1N1 vaccination may reflect the underlying host immune response. However, further work to elucidate the sources of the exhaled breath changes is necessary.

Exhaled nitric oxide in asthma in adults: the end is the beginning?

Approximately 20 years after the initial report of the measurement of exhaled nitric oxide (NO) in the exhaled air of humans, numerous publications have evaluated the possible applications of the fraction of exhaled NO (FeNO) in patients with asthma. The aim of the present review is to evaluate the technical issues and confounding factors related to FeNO measurements, as well as the role of FeNO in the diagnosis of asthma, the evaluation of asthmatic patients and the guidance of treatment. Several other issues, including the pursuit for "normal" and best personal values, the prediction of clinically relevant asthma outcomes and the identification of asthma phenotypes and future directions are discussed. FeNO represents the only exhaled biomarker that has reached clinical practice even in primary care settings and this review provides a critical view of the possible applications of this biomarker, both for the basic researcher and the clinician.

Biomarkers in exhaled breath condensate: a review of collection, processing and analysis.

Exhaled breath condensate (EBC) is a potential rich source for countless biomarkers that can provide valuable information about respiratory as well as systemic diseases. EBC has been studied in a variety of diseases including allergic rhinitis, asthma, chronic obstructive lung disease, cystic fibrosis, lung cancer, and obstructive sleep apnea syndrome. Although numerous biomarkers have been discovered and studied in EBC, the methods of collection and biomarker detection have not been fully standardized. While leaving standardization methods up to individual labs for the present time is optimal for the continued discovery of new biomarkers in EBC, this decreases the reproducibility and generalizability of the findings. In this review we will discuss specific biomarkers studied in specific diseases as well as some of the related technical issues including collection, processing and analysis.

Exhaled breath condensate: methodological recommendations and unresolved questions.

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Alterations in exhaled gas profile during allergen-induced asthmatic response.

The source of exhaled carbon monoxide (CO) and the relationship to airway inflammation are not clear. If CO is produced by the inflamed airway, we hypothesized that inflammation induced by allergen challenge would increase exhaled CO of atopic asthmatics. Eight atopic asthmatics underwent whole lung allergen challenge. CO, nitric oxide (NO), oxygen, and carbon dioxide (CO(2)) were measured simultaneously in exhaled breath which was collected into Mylar balloons before (baseline), immediately after, and at subsequent times after allergen. NO was higher in asthmatics than control subjects at baseline, increased further in seven of the eight asthmatics after allergen, and was inversely correlated to specific conductance. In contrast, exhaled CO of asthmatics was not higher than that of control individuals at baseline, decreased immediately after allergen, and returned to baseline levels during the late asthmatic response. Thus, allergen-induced airway inflammation did not lead to increased exhaled CO in asthma.

Major histocompatibility locus genetic markers of beryllium sensitization and disease.

Hypersensitivity to beryllium (Be) is found in 1-16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only approximately 50% of BeLPT-positive workers present with lung granulomas (i.e. berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation. A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-alpha polymorphism TNF-alpha-308 in 23 individuals presenting as "sensitized" (i.e. BeLPT-positive without lung granulomas) and in 22 presenting as "diseased" (i.e. BeLPT-positive with granulomas in the lung biopsy). The HLA-DPGlu69 marker was associated with "disease" (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4-10.0), whilst the high TNF-alpha production-related TNF-alpha-308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2-19.1) with no difference between "sensitization" and "disease". Furthermore, the HLA-DRArg74 marker was associated with "sensitization" without disease (OR 3.96, p=0.005, 95%, CI 1.5-10.1). The data indicate that tumour necrosis factor-alpha, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.

Drug-induced lung disease.

Drug-induced lung disease is a major source of iatrogenic injury. We review the various drugs known to induce injury and the various patterns of injury seen.

The promise and reality of nitric oxide in the diagnosis and treatment of lung disease.

Endogenously produced nitric oxide plays a major role in lung physiology and pathology. Inhaled nitric oxide given exogenously has been studied extensively as a treatment for many lung diseases, and the results suggest that it may help improve oxygenation in some patients. Several issues need to be addressed, however, before it can be used in routine clinical practice.

High levels of exhaled nitric oxide (NO) and NO synthase III expression in lesional smooth muscle in lymphangioleiomyomatosis.

Smooth-muscle proliferation is the hallmark of lymphangioleiomyomatosis (LAM). Although little is known about the pathogenesis of LAM, nitric oxide (NO) is a key regulator of smooth-muscle proliferation. NO is linked to the pathogenesis of other lung diseases such as asthma, in part by the finding of higher-than-normal levels of exhaled NO. If NO were involved in the abnormal smooth-muscle proliferation in LAM, we reasoned that exhaled NO from individuals with LAM would also differ from that of healthy control subjects. To evaluate this hypothesis, we studied exhaled NO in individuals with LAM in comparison with healthy and asthmatic women using a chemiluminescent NO analyzer. Women with LAM had higher exhaled NO than did healthy women but lower than asthmatic women (NO [parts per billion] median (25 to 75%): LAM 8 [7 to 15] [n = 28], control 6 [5 to 8] [n = 21], asthma 14 [8 to 25] [n = 22]; Kruskal-Wallis P < 0.001). Immunohistochemical studies on formalin-fixed, paraffin-embedded sections of surgical and autopsy material from lungs of individuals with LAM showed diffuse NO synthase III (NOSIII) expression in the lesional smooth muscle of LAM similar to that in the vascular endothelium. NOSIII expression was limited to the vascular endothelium and bronchial smooth muscle in healthy control lungs. The increased NO and the presence of NOSIII expression in lesional smooth muscle warrants further study into the potential role for NO in the pathogenesis of LAM.

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response.

A wealth of evidence supports increased NO (NO.) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was the only NO. derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO. dynamics derived from the current findings predicts that NO. may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO. derivatives.

High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy.

Lack of vasodilator substances, such as nitric oxide (NO), has been implicated in the development of pulmonary hypertension, but the pathogenesis of the disease remains speculative. We hypothesized that NO plays a role in the pathogenesis of primary pulmonary hypertension (PPH), and may serve as a sensitive and specific marker of disease progression and/or severity. To test this, exhaled NO and pulmonary artery pressure were measured in individuals with PPH and secondary pulmonary hypertension (SPH) on various therapies, including the potent vasodilator epoprostenol (prostacyclin), compared with healthy controls. NO in exhaled breath of individuals with PPH was lower than SPH or control (p<0.05). In contrast, exhaled NO of individuals with PPH or SPH receiving epoprostenol was strikingly higher than PPH or SPH individuals not receiving epoprostenol, or controls. Concomitant with higher NO levels, right ventricular systolic pressure of individuals significantly decreased with epoprostenol. Importantly, in paired measures of exhaled NO before and after epoprostenol, NO increased in all pulmonary hypertensive individuals 24 h after initiation of epoprostenol therapy (p<0.05). NO may be a useful noninvasive marker of pulmonary hypertension severity and response to prostacyclin therapy.

A 65-year-old factory worker with dyspnea on exertion and a normal chest x-ray.

Chronic beryllium disease is an occupationally acquired granulomatous lung disease similar to sarcoidosis. It is caused by exposure to beryllium in genetically susceptible persons. It should be suspected in patients with beryllium exposure who present with pulmonary symptoms or have a positive screening blood beryllium-specific lymphocyte proliferation test. The diagnosis is confirmed by the finding of granulomas on transbronchial biopsy in the appropriate clinical and epidemiologic setting. Although there is no cure, treatment with corticosteroids is usually beneficial. In view of the potential side effects, treatment is reserved for patients with symptoms or a decline in pulmonary function.