Feasibility Study on the Use of NO2 and PM2.5 Sensors for Exposure Assessment and Indoor Source Apportionment at Fixed Locations.

Recent advances in sensor technology for air pollution monitoring open new possibilities in the field of environmental epidemiology. The low spatial resolution of fixed outdoor measurement stations and modelling uncertainties currently limit the understanding of personal exposure. In this context, air quality sensor systems (AQSSs) offer significant potential to enhance personal exposure assessment. A pilot study was conducted to investigate the feasibility of the NO2 sensor model B43F and the particulate matter (PM) sensor model OPC-R1, both from Alphasense (UK), for use in epidemiological studies. Seven patients with chronic obstructive pulmonary disease (COPD) or asthma had built-for-purpose sensor systems placed inside and outside of their homes at fixed locations for one month. Participants documented their indoor activities, presence in the house, window status, and symptom severity and performed a peak expiratory flow test. The potential inhaled doses of PM2.5 and NO2 were calculated using different data sources such as outdoor data from air quality monitoring stations, indoor data from AQSSs, and generic inhalation rates (IR) or activity-specific IR. Moreover, the relation between indoor and outdoor air quality obtained with AQSSs, an indoor source apportionment study, and an evaluation of the suitability of the AQSS data for studying the relationship between air quality and health were investigated. The results highlight the value of the sensor data and the importance of monitoring indoor air quality and activity patterns to avoid exposure misclassification. The use of AQSSs at fixed locations shows promise for larger-scale and/or long-term epidemiological studies.

Health effects of heating, ventilation and air conditioning on hospital patients: a scoping review.

BACKGROUND: In the face of climate change, the protection of vulnerable patients from extreme climatic conditions is of growing interest to the healthcare sector and governments. Inpatients are especially susceptible to heat due to acute illness and/or chronic diseases. Their condition can be aggravated by adverse environmental factors. Installing air conditioning can be seen as an element of public health adaptation because it was shown to improve mortality rates of hospital patients experiencing hot temperatures. Still, the mediating factors and resulting health effects are largely unknown. METHOD: The PRISMA-ScR guideline was followed for this scoping review. Available evidence on the health effects of Heating, Ventilation, Air Conditioning (HVAC) and fans was searched in Medline, Embase and the Cochrane Library. The focus of the search strategy was on inpatients of the hospital. Grey literature was screened on 14 relevant websites. English and German publications were eligible without restrictions on publication date. Results were charted according to the categories population, intervention, control and outcome together with a qualitative description. RESULTS: The review process yielded eleven publications of which seven were issued after 2003. Seven were clinical trials, three cross-sectional studies and one was a case report. The publications described the installation of HVAC on general wards and in intensive care units. Main topics were heat stress protection and support of thermoregulation, but also the rewarming of hypothermic patients. HVAC use resulted in a recovery effect shown by improved vital signs, reduced cardiac stress, accelerated recuperation and greater physical activity. This protective effect was demonstrated by a shorter hospital stay for patients with respiratory disease and a reduction of mortality for heat illness patients. CONCLUSION: This scoping review summarises the fragmented evidence on health effects of HVAC and fan utilisation for inpatients. Installing HVAC has the potential to improve patients' outcomes and to make hospital treatment more efficient during heat waves. The application of HVAC could be a promising adaptation measure to mitigate the adverse effects of climate change on health and healthcare systems.

Radiologic manifestations of bronchoscopic lung volume reduction in severe chronic obstructive pulmonary disease.

OBJECTIVE. Bronchoscopic lung volume reduction promises to become an effective treatment option in severe chronic obstructive pulmonary disease. Several techniques are currently being investigated, including implantation of devices into the lung and instillation of hot water vapor or polymer. This article reviews the spectrum of radiologic manifestations on chest radiography and CT that occur after the intervention. CONCLUSION. Familiarity with the intended effects and adverse events will aid the radiologist in supporting bronchoscopic lung volume reduction.

Heat stress is associated with reduced health status in pulmonary arterial hypertension: a prospective study cohort.

BACKGROUND: Summer heat waves with temperature extremes are becoming more frequent with growing numbers in morbidity and mortality in patients with respiratory diseases. The aim of this study was to evaluate the ramifications of heat stress (temperature >25 °C) on the health status of patients with pulmonary arterial hypertension (PAH). METHODS: Fifteen patients with PAH (mean age = 66.7 ± 5.2 years) continuously wore an accelerometer from April 1 to September 30, 2011, and their daily step count was recorded. In addition, patients kept a diary to record data on seven standardized questions regarding their daily symptoms. Echocardiography, 6-minute walk test, NTproBNP, and Modified Medical Research Council Scale (MMRC) were assessed at baseline and at the end of the study after 6 months. RESULTS: On heat-stress days, patients showed significantly more symptoms and lower total steps/day compared to thermal comfort days (3,995 ± 2,013 steps/day vs. 5,567 ± 2,434 steps/day, respectively; P < 0.001). There was a significant negative correlation between total steps/day and Temp(max) (R = -0.47; P < 0.001) and humidity (R = -0.34; P < 0.001). A significant positive correlation was found between daily symptoms and Temp(max) (R = +0.79; P < 0.001) and humidity (R = +0.23; P < 0.001). CONCLUSIONS: Heat stress is associated with a compromised clinical status in patients with PAH. Adaptation strategies must be implemented to prevent heart-related morbidity, including therapeutic adjustments and adequate room cooling in the patient's home and at the hospital.

Tele-monitoring reduces exacerbation of COPD in the context of climate change--a randomized controlled trial.

BACKGROUND: A home based tele-monitoring system was developed to assess the effects of heat stress (days > 25°C) on clinical and functional status in patients with chronic obstructive pulmonary disease (COPD). METHODS: Sixty-two COPD patients (GOLD II-IV) were randomized into a tele-monitoring Group (TG, N = 32) or Control Group (CG, N = 30). Tele-monitoring included 1) daily clinical status (COPD Assessment Test-CAT), 2) daily lung function and 3) weekly 6-minute walk test (6MWT). Duration of monitoring lasted a total of nine months (9 M). RESULTS: From June 1st-August 31st 2012, 32 days with heat stress (29.0 ± 2.5°C) were recorded and matched with 32 thermal comfort days (21.0 ± 2.9°C). During heat stress, the TG showed a significant reduction in lung function and exercise capacity (FEV1% predicted: 51.1 ± 7.2 vs. 57.7 ± 5.0%; P <0.001 and 6MWT performance: 452 ± 85 vs. 600 ± 76 steps; P <0.001) and increase in CAT scores (19.2 ± 7.9 vs. 16.2 ± 7.2; P <0.001).Over summer, significantly fewer TG patients suffered exacerbation of COPD compared to CG patients (3 vs. 14; P = 0.006). Over entire 9 M follow-up, the TG group had fewer exacerbations compared to CG (7 vs. 22; P = 0.012), shorter cumulative hospital stay (34 vs. 97 days) and 43% fewer specialist consultations (24. vs. 42; P = 0.04). CONCLUSION: Heat stress affects clinical and functional status in COPD. Tele-monitoring reduces exacerbation frequency and health care utilization during heat stress and other periods of the year. TRIAL REGISTRATION DRKS-ID: DRK00000705.

Long-term indoor gunshot exposure of special police forces induces bronchitic reactions and elevated blood lead levels-The Berlin shooting range study.

BACKGROUND: Gunshot emissions contain toxic elements that can harm those frequently exposed, such as police officers. Several years ago, police indoor firing ranges were closed by the Berlin municipality in response to police officer health complaints, and an investigation was launched into the possible respiratory health risks of frequent gunshot emission exposure. We, therefore, conducted an exploratory cross-sectional study to investigate clinical and functional parameters of respiratory health as well as the burden of trace elements in policemen with long-term high exposure to indoor gunshot emissions, compared to low-exposure and control groups. METHODS: We conducted lung function tests and collected blood and urine samples from Berlin police officers and government employees who were divided into three subject groups based on exposure to gunshot emissions: high exposure (n = 53), low exposure (n = 94) and no exposure (n = 76). Lung function was examined using body plethysmography. Blood and urine samples were tested via inductively coupled plasma mass spectrometry for the presence of common gunshot powder elements (antimony, lead and manganese). Exposure and symptoms were assessed using records as well as questionnaires. RESULTS: Higher exposure was associated with more respiratory symptoms during gun shooting practice (64% vs. 21%, P < 0.001) compared to the low-exposure group. Headache, cough, discoloured mucous and shortness of breath were also more common as were some other symptoms. The cough symptomatology of the high-exposure group also persisted significantly longer (median: 0.67 vs. 0.01 days, range: 0 to 5 days, P = 0.029) compared to the low-exposure group. They also showed a lower forced expiratory volume in 1 s/forced vital capacity quotient (Tiffeneau index), P = 0.018 between the three groups and P = 0.005 for the high-exposure group, a possible marker of early, subclinical bronchial obstruction. We observed increased blood lead concentrations depending on subject's age (+1.2% per year, 95% confidence interval: 0.5-1.9%, P < 0.001) and cumulative gunshot exposure (+0.34% per 100 000 shots, 0.02-0.66%, P = 0.037). CONCLUSIONS: These first results suggest that long-term exposure to indoor gunshot emissions induces bronchitic reactions due to repeated irritation of the airways. Higher levels of exposure lead to more negatively impacted lung function and higher blood lead levels with the possible reason that more frequent exposure may mean shorter regeneration phases for the respiratory mucous membrane. We recommend a reduction of exposure to gunshot emissions in order to decrease symptoms and avoid any-even small-deterioration in spirometry.

A Qualitative Study on Concerns, Needs, and Expectations of Hospital Patients Related to Climate Change: Arguments for a Patient-Centered Adaptation.

This study explores the concerns, needs, and expectations of inpatients with the goal to develop a patient-centered climate change adaptation agenda for hospitals. Statements of patients from geriatrics, internal medicine, psychiatry, and surgery (N = 25) of a German tertiary care hospital were analyzed using semi-structured interviews and the framework method. Areas of future adaptation were elaborated in joint discussions with transdisciplinary experts. Concerns included the foresight of severe health problems. The requested adaptations comprised the change to a patient-centered care, infrastructural improvements including air conditioning, and adjustments of the workflows. Guidelines for the behavior of patients and medical services appropriate for the climatic conditions were demanded. The patient-centered agenda for adaptation includes the steps of partnering with patients, reinforcing heat mitigation, better education for patients and medical staff, and adjusting work processes. This is the first study demonstrating that hospital patients are gravely concerned and expect adjustments according to climate change. Since heat is seen as a major risk by interviewees, the fast implementation of published recommendations is crucial. By synthesizing inpatients' expectations with scientific recommendations, we encourage patient-centered climate change adaptation. This can be the start for further collaboration with patients to create climate change resilient hospitals.

An adaptation strategy to urban heat: hospital rooms with radiant cooling accelerate patient recovery.

BACKGROUND: Patients with respiratory diseases are vulnerable to the effects of heat. Therefore, it is important to develop adaptation strategies for heat exposure. One option is to optimise the indoor environment. To this end, we equipped hospital patient rooms with radiant cooling. We performed a prospective randomised clinical trial to investigate potentially beneficial effects of the hospitalisation in rooms with radiant cooling on patients with a respiratory disease exacerbation. METHODS: Recruitment took place in June, July and August 2014 to 2016 in the Charité - Universitätsmedizin Berlin, Germany. We included patients with COPD, asthma, pulmonary hypertension, interstitial lung disease and pneumonia. 62 patients were allocated to either a standard patient room without air conditioning or a room with radiant cooling set to 23°C (73°F). We analysed the patients' length of stay with a Poisson regression. Physiological parameters, fluid intake and daily step counts were tested with mixed regression models. RESULTS: Patients hospitalised in a room with radiant cooling were discharged earlier than patients in standard rooms (p=0.003). The study participants in chambers with radiant cooling had a lower body temperature (p=0.002), lower daily fluid intake (p<0.001), higher systolic blood pressure (p<0.001) and an increased daily step count (p<0.001). CONCLUSION: The results indicate that a radiant cooling system in hospital patient rooms provides clinical benefits for patients with respiratory disease exacerbations during the warm summer months, which may contribute to an earlier mobilisation. Radiant cooling is commended as a suitable adaptation strategy to reduce the clinical impact of climate warming.

Can nasal acetylsalicylic acid challenge predict the severity of non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD)?
.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD) complicates the clinical course of chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma. We aimed to determine the detection rate of NERD in patients with CRSwNP, asthma, and history of NSAID intolerance using nasal challenge with acetylsalicylic acid (ASA) and the relationship between the severities of response to ASA challenges and the grade of N-ERD. MATERIALS AND METHODS: Three groups of patients were included: CRSwNP with asthma and clinical history of analgesics intolerance (CRSwNP-AAI n = 18), CRSwNP with asthma but without a clinical history of analgesics intolerance (CRSwNP-A n = 20), and CRSwNP without asthma or analgesics intolerance (n = 18). All subjects were challenged nasally with 16 mg ASA and monitored with active anterior rhinomanometry. Rhinological (nasal polyp score), pulmonary (spirometry, Asthma Control Test (ACT), and asthma treatment), and psychometric questionnaire scores were recorded and correlated with rhinomanometric data following nasal challenges (flow depressions and symptom scores). RESULTS: Nasal ASA challenge detected N-ERD in 96.7% of CRSwNP-AAI patients and 45% of CRSwNP-A patients. No N-ERD was seen in the CRSwNP group. The control grade of asthma measured with ACT scores was significantly lower in the groups CRSwNP-AAI (MV 18.22) and CRSwNP-A (MV 19.75) when compared to the CRSwNP group (MV 24.39) (p = 0.000). In the CRSwNP-AAI group, 11 patients had uncontrolled asthma (61%), and in the CRSwNP-A group, 9 patients had uncontrolled asthma (45%). No correlation was found between rhinology and pulmonary parameters, nasal symptoms, and the severity of nasal ASA challenges. Specific reactions were detectable under the therapy of prednisolone and omalizumab. CONCLUSION: N-ERD might not always be detected by screening a patient's medical history. Nasal ASA challenges are recommended in patients with CRSwNP and asthma. The nasal challenge with ASA positively confirms the N-ERD diagnosis. Moreover, N-ERD is a differential diagnosis in patients with severe asthma with the need for prednisolone or omalizumab therapy. The severity of the reaction to the ASA challenge in controlled and uncontrolled asthma patients is independent of the grade of N-ERD.
.

Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations.

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by perturbed or absent beating of motile cilia, which is referred to as Kartagener syndrome (KS) when associated with situs inversus. We present a German family in which five individuals have PCD and one has KS. PCD was confirmed by analysis of native and cultured respiratory ciliated epithelia with high-speed video microscopy. Respiratory ciliated cells from the affected individuals showed an abnormal nonflexible beating pattern with a reduced cilium bending capacity and a hyperkinetic beat. Interestingly, the axonemal ultrastructure of these respiratory cilia was normal and outer dynein arms were intact, as shown by electron microscopy and immunohistochemistry. Microsatellite analysis indicated genetic linkage to the dynein heavy chain DNAH11 on chromosome 7p21. All affected individuals carried the compound heterozygous DNAH11 mutations c.12384C>G and c.13552_13608del. Both mutations are located in the C-terminal domain and predict a truncated DNAH11 protein (p.Y4128X, p.A4518_A4523delinsQ). The mutations described here were not present in a cohort of 96 PCD patients. In conclusion, our findings support the view that DNAH11 mutations indeed cause PCD and KS, and that the reported DNAH11 nonsense mutations are associated with a normal axonemal ultrastructure and are compatible with normal male fertility.

Increased vulnerability of COPD patient groups to urban climate in view of global warming.

PURPOSE: Patients with COPD show an increase in acute exacerbations (AECOPD) during the cold season as well as during heat waves in the summer months. Due to global climate changes, extreme weather conditions are likely to occur more frequently in the future. The goal of this study was to identify patient groups most at risk of exacerbations during the four seasons of the year and to determine at which temperature threshold the daily hospital admissions due to AECOPD increase during the summer. PATIENTS AND METHODS: We analyzed retrospective demographic and medical data of 990 patients, who were hospitalized for AECOPD in Berlin, Germany. The cases were grouped into the following cohorts: "spring" (admission between March and May), "summer" (June - August), "autumn" (September - November), and "winter" (December - February). AECOPD hospital admissions from 2006 and 2010 were grouped into a "hot summer" cohort and cases from 2011 and 2012 into a "cold summer" data-set. Climate data were obtained from the German Meteorological Office. RESULTS: Patients hospitalized for a COPD exacerbation during winter were significantly older than summertime patients (P=0.040) and also thinner than patients exacerbating in spring (P=0.042). COPD exacerbations during hot summer periods happened more often to patients with a history of myocardial infarction (P=0.014) or active smokers (P=0.011). An AECOPD during colder summers occurred in patients with a higher Charlson index, who suffered in increased numbers from peripheral vascular diseases (P=0.016) or tumors (P=0.004). Summertime hospital admissions increased above a daily minimum temperature of 18.3°C (P=0.006). CONCLUSION: The identification of COPD patient groups most at risk for climate related exacerbations enables climate-adapted prevention through patient guidance and treatment. In view of global climate changes, discovering vulnerabilities and implementing adaptive measures will be of growing importance.

Segmental volume reduction using thermal vapour ablation in patients with severe emphysema: 6-month results of the multicentre, parallel-group, open-label, randomised controlled STEP-UP trial.

BACKGROUND: Lung volume reduction of emphysematous lobes results in clinical improvement for patients with severe emphysema. However, some segments within a lobe are often substantially more diseased than others, thereby warranting a more targeted approach of the emphysematous parts of a lobe. We therefore did a study to assess whether or not selective sequential treatment of the more diseased upper lobe segments with bronchoscopic vapour ablation led to clinical improvement. METHODS: For the multicentre, parallel-group, randomised, controlled, open-label Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial, adult patients aged 45-75 years with severe, upper lobe-predominant emphysema with a forced expiratory volume in 1 s (FEV1) between 20% and 45%, substantial hyperinflation, and post-rehabilitation 6-min walk test (6MWT) greater than 140 m were enrolled from 13 hospital sites in Europe (ten sites) and Australia (three sites). A computer-generated blocked randomisation scheme (block size three per site based on a random table from an independent biostatistician) stratified by site was used to randomly assign enrolled patients 2:1 to segmental vapour ablation (treatment group) or standard medical management (control group). Patients and investigators were not masked to group assignment. The primary efficacy endpoints were statistically significant changes in FEV1 and St George's Respiratory Questionnaire (SGRQ-C) scores between trial groups at 6 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01719263. FINDINGS: Between June 30, 2013, and Oct 1, 2014, 134 patients were screened and 70 were enrolled and randomly assigned: 46 to the treatment group and 24 to the control group. One patient in the treatment group did not receive treatment because of physician decision post-randomisation; this patient is excluded from all analyses. The mean relative improvement in FEV1 between the treatment group versus the control group was 14·7% (95% CI 7·8-21·5%; p<0·0001) and in SGRQ-C was -9·7 points (95% CI -15·7 to -3·7; p=0·0021). COPD exacerbation was the most common serious adverse event, occurring in 11 (24%) of 45 patients in the treatment group and one (4%) of 24 in the control group. One exacerbation resulted in a patient death 84 days after treatment; this was judged by the data and safety monitoring board to be possibly related to treatment. No pneumothorax occurred within 30 days of treatment. INTERPRETATION: Compared with standard medical management, targeted thermal vapour ablation of more diseased segments and preservation of less diseased segments resulted in clinically meaningful and statistically significant improvements in lung function and quality of life at 6 months, with an acceptable safety profile. FUNDING: Uptake Medical.

Infection of cells with replication deficient adenovirus induces cell cycle alterations and leads to downregulation of E2F-1.

Gene products of recombinant replication-deficient adenovirus vectors of the first generation (Ad vector) can induce cell cycle dysregulation and apoptosis after infection in eukaryotic cells. The mechanisms underlying this complex process are largely unknown. Therefore, we investigated the regulation of the pRb/E2F-1 complex, which controls transition from G(0)/G(1) to S phase of the cell cycle. As Ad vector infection results in a decrease in the number of cells in G(0)/G(1) phase of the cell cycle, we observed a decline of the pRb protein level and, surprisingly, also a decrease of the E2F-1 protein and mRNA level in infected cell lines. Furthermore, in contrast to the reduction of cells in the G(0)/G(1) phase we observed increased protein levels of p53 and p21 proteins. However, as experiments in p53 deficient cell lines indicated, the decrease of pRb and E2F-1 is independent of p53 and p21 expression. Moreover, results obtained with Rb deficient cell lines indicated that the reduced E2F-1 expression is independent of pRb. These results suggest that Ad vector-induced cell cycle dysregulation is associated with a specific downregulation of E2F-1 independent of Rb and p53 genomic status of cells.

The Effects of Climate Change on Patients With Chronic Lung Disease. A Systematic Literature Review.

BACKGROUND: Ever since higher overall mortality rates due to heat stress were reported during the European heat waves of 2003 and 2006, the relation between heat waves and disease-specific events has been an object of scientific study. The effects of heat waves on the morbidity and mortality of persons with chronic lung disease remain unclear. METHODS: We conducted a systematic search using PubMed, the Cochrane Library, and Google Advanced Search to identify relevant studies published between 1990 and 2015. The reference lists of the primarily included articles were searched for further pertinent articles. All articles were selected according to the PRISMA guidelines. The heat-wave-related relative excess mortality was descriptively expressed as a mean daily rate ratio ([incidence 1]/[incidence 2]), and the cumulative excess risk (CER) was expressed in percent. RESULTS: 33 studies with evaluable raw data concerning the effect of heat waves on patients with chronic lung disease (chronic obstructive pulmonary disease, bronchial asthma, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis) were analyzed in this review. By deriving statistics from the overall data set, we arrived at the conclusion that future heat waves will-with at least 90% probability-result in a mean daily excess mortality (expressed as a rate ratio) of at least 1.018, and-with 50% probability-in a mean daily excess mortality of at least 1.028. These figures correspond, respectively, to 1.8% and 2.8% rises in the daily risk of death. CONCLUSION: Heat waves significantly increase morbidity and mortality in patients with chronic lung disease. The argument that the excess mortality during heat waves is compensated for by a decrease in mortality in the subsequent weeks/months (mortality displacement) should not be used as an excuse for delay in implementing adaptive strategies to protect lung patients from this risk to their health.