Lung DOI 10.1007/s00408-014-9587-4
Heat Stress is Associated with Reduced Health Status in Pulmonary Arterial Hypertension: A Prospective Study Cohort Melissa Jehn • Andreas Gebhardt • Uta Liebers • Bahar Kiran • Dieter Scherer • Wilfried Endlicher Christian Witt
•
Received: 25 November 2013 / Accepted: 11 April 2014 Ó European Union 2014
Abstract 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 M. Jehn (&) A. Gebhardt U. Liebers B. Kiran C. Witt (&) Division of Pneumological Oncology and Transplantology, Charite´ Universita¨tsmedizin Berlin, Campus Charite´ Mitte, Charite´platz 1, 10117 Berlin, Germany e-mail: [email protected] C. Witt e-mail: [email protected] D. Scherer Institute for Ecology, Technische Universita¨t Berlin (on behalf of the UCaSH Research Group), Berlin, Germany W. Endlicher Geography Department, Humboldt-Universita¨t zu Berlin (on behalf of the KLIMZUG Research Group), Berlin, Germany
significant negative correlation between total steps/day and Tempmax (R = -0.47; P \ 0.001) and humidity (R = -0.34; P \ 0.001). A significant positive correlation was found between daily symptoms and Tempmax (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. Keywords Vulnerability Heat stress Exacerbation frequency Activity monitoring
Introduction With global warming, extreme temperature changes (both hot and cold) will become more frequent, and, in particular, heat waves will last longer and be more intense [1, 2]. How this will affect human health, especially that of patients with pulmonary arterial hypertension (PAH), is poorly understood at present. PAH is a rare lung disease characterized by reduced quality of life and overall poor patient outcome [3]. Epidemiological studies show an increase in morbidity and mortality on hot days among patients with respiratory diseases, including PAH [4–7]. Nevertheless, little is known about the clinical and functional consequences of heat stress in patients with PAH, in particular, the degree of physical impairment [6]. Exercise capacity is an integral component in the clinical evaluation of PAH patients, because the degree of physical impairment strongly correlates with clinical prognosis. Continuous ambulatory activity measured by an accelerometer is a surrogate marker of functional exercise
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capacity in patients with chronic diseases [8, 9]. The analysis of daily activity patterns over time, including the amount of sedentary time, enables clinicians to evaluate therapy more thoroughly [10]. The multidisciplinary German Federal Research Program KLIMZUG (‘‘Klima in Regionen zukunftsfa¨hig gestalten’’) aims to investigate adaptation strategies to climate change in Berlin, Germany, a metropolitan midlatitude area surrounded by the countryside of Brandenburg (trial registration: DRKS-ID: DRK00000705). One of the working goals of this project is to assess the degree of medical vulnerability of PAH patients susceptible to heat stress, including their clinical status, exercise capacity, and subsequent therapeutic measures. The primary aim of this study is to evaluate whether exposure to heat stress is associated with a reduction in functional capacity of patients with PAH measured by means of daily symptoms and accelerometer-based physical activity levels. Methods Fifteen clinically stable patients diagnosed with PAH were included in this study [11]. Clinical diagnosis of PAH was based of clinical history, physical examination, echocardiography, and right-sided heart catheterization, with mean pulmonary artery pressure [ 25 mmHg at rest and capillary wedge pressure \ 15 mmHg [12]. Inclusion criterion was New York Heart Association (NYHA) functional class II–IV. Exclusion criterion was having any malignant disease, particularly one that limits exercise tolerance such as chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), or rheumatoid arthritis. Patients were also excluded if they had any severe musculoskeletal disorders that prevented them from walking without assistance. Patients had an initial baseline examination and a follow-up exam at 6 months. Assessments included detailed medical history, duration of PAH, comorbidities, physical examination, spirometry, 6-minute walk test, NTproBNP, and systolic pulmonary artery pressure (sPAP). The Modified Medical Research Council (MMRC) Dyspnea Scale was assessed at baseline and then once a month for the 6 months of the study. Patients were categorized according to functional classes II– IV based on their level of exercise tolerance, with a higher functional class (FC) indicating greater disease severity. The study was carried out according to the principles of the Declaration of Helsinki and approved by our local ethics committee (Ethics No. EA1/033/10). Written informed consent was obtained from all participating patients.
to wear the device throughout the day from April 1 to September 30 while going about their daily business. The device was attached to the patient’s belt and positioned above the left hip. Patients were instructed to attach the device upon rising in the morning and to take it off only for showering, bathing, and sleeping. Activity data were recorded continuously (24 h) and the time when it was not worn was indicated as ‘‘resting mode.’’ All device settings were preprogrammed for each patient and the device was ‘‘on’’ throughout the entire measurement period to keep handling of the accelerometer by the patient to a minimum. The screen display was set to ‘‘standby’’ mode to hide data analysis. Therefore, patients did not receive any direct feedback from the device regarding their daily activity time, energy expenditure, distance, or number of steps taken. Upon return of the accelerometer, the data were downloaded onto a PC and viewed via the ActiCoach MPAT2Viewer program (Aipermon). Wearing time included min/day spent passively (i.e., sitting), actively (i.e., moving but not walking), walking (0–5 km/h or 0–80 m/min), and fast walking ([5 km/h or 81–115 m/min), steps, calories, and distance (m). The device used was a three-dimensional accelerometer that measures movement continuously in three axes (x, y, z). Data output is provided in 60-s intervals for each consecutive day (24 h), with the exact time and date for each epoch. Activity modes and accelerometer detection accuracy were extensively validated and detailed results are reported elsewhere [13]. In summary, the device was able to detect steps to 99 % accuracy at walking speeds as low as 20 m/min. The thresholds used to classify walking speeds are set by the manufacturer and based on the walking behavior of older individuals with heart failure [13, 14], a patient population for which it was originally designed using a large multicenter study that investigated the feasibility of remote patient telemonitoring [15–17]. Daily Symptoms Score The questions of the daily symptom score were adapted directly from the COPD Assessment Test (CAT). The questionnaire consisted of seven questions that were weighed on a scale of 0–5, with higher scores indicating worse symptoms. Question referred to (1) impairment in daily activities, (2) breathlessness going up stairs, (3) worries about leaving the house, (4) quality of sleep, (5) energy level, (6) occurrence of cyanosis related to lung disease, and (7) existence of edema. Scores given to individual questions were added up for a total score for each day, which was used for all subsequent analyses.
Accelerometer Activity Monitoring
Assessment of Temperature Data
Patients were given an accelerometer (Aipermon GmbH, Munich, Germany) during their baseline visit and instructed
Data regarding daily temperature (in °C) were obtained from the local weather station (Tempelhof, Berlin, Germany;
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maintained by the Deutscher Wetterdienst) and included daily temperature readings (Tempmean, Tempmax, Tempmin), air pressure (hPa), and humidity (%). This weather station is located 48 m above normal null (NN) at 52.47° N 13.4° E. Days when the Tempmax C 25 °C were considered ‘‘heatstress days,’’ whereas days when the Tempmax \ 25 °C were regarded as ‘‘thermal-comfort days.’’ To combine temperature and humidity, the following formula was applied: temperature 9 humidity (%) /100. Statistical Analysis Statistical analysis was performed using SPSS software ver. 21.0 (SPSS Inc., Chicago, IL, USA). Data were descriptively analyzed and reported as mean ± standard deviation (SD) for quantitative measurements and percentages for frequencies. Bivariate correlations of nonparametric variables were investigated using Spearman-Rho correlation coefficient (R). Differences between heat-stress and thermalcomfort days were compared using a paired Student’s t test for normally distributed variables. P values less than 0.05 were considered statistically significant. Scatter plots were used to illustrate the association of temperature and humidity with daily activity levels and symptoms score. Box plots and bar graphs were used to illustrate the influence of daily climate data on clinical parameters, including daily activity levels and symptoms score.
Results Patient Characteristics Baseline patient characteristics are given in Table 1. Mean changes from the baseline parameters to 6-month follow-up were ?13.2 ± 64.6 m in 6-min walk test distance, ?32.4 ± 775 pg/ml in NTproBNP, ?2.8 ± 10.73 mmHg in sPAP, -0.1 ± 1.02 in the MMRC Dyspnea Scale, and ?2.2 ± 1.78 % in FEV1 (%). Patients walked an average of 4,998 ± 2,229 steps/day and had a symptom score of 14.6 ± 7.2 points over the 6-month monitoring period. Total steps per day showed a significant positive correlation with the 6-min walking distance at baseline and at the 6-month follow-up (R = ?0.79 and ?0.71, respectively; P \ 0.001). Finally, change in mean pulmonary arterial pressure was significantly associated with changes in NTproBNP levels, both at baseline and the 6-month follow-up (R = ?0.79 and ?0.88, respectively; P \ 0.001). Monitoring Period (April 1–September 30, 2011) Between April 1 and September 30, 2011, there were 65 heatstress days and 118 thermal-comfort days. On heat-stress
Table 1 Patient characteristics at baseline N
15
Gender (male/female)
9/6
Age (years)
63.5
BMI (kg/m2)
28.9 ± 14.8
FEV1 (%)
61.7 ± 19.1
NYHA functional class
NYHA II = 5 NYHA III = 10
MMRC
3.5 ± 1.08
sPAP (mmHg)
65.8 ± 14.5
NTproBNP (pg/ml)
1016 ± 1131
6MWT (m)
287 ± 93.7
SpO2 saturation during 6MWT
86.0 ± 2.8
HR during 6MWT
112.2 ± 8.9
Medication Oral anticoagulation Iloprost
10 (67 %) 6 (40 %)
Phosphodiesterase-5 inhibitor
8 (53 %)
Endothelin receptor antagonist
12 (80 %)
Long term O2 therapy
15 (100 %)
Data are presented as mean ± SD and frequencies (%) 6MWT 6-minute walk test, sPAP systolic pulmonary artery pressure, MMRC Modified Medical Research Council, BMI body mass index, FEV1 forced expiratory volume in 1 second, NYHA New York Heart Association functional class, SpO2 oxygen saturation
days, the temperature according to the German Weather Service reached an average Tempmax of 27.0 ± 2.0 °C with relative humidity of 66 %. Thermal-comfort days had a mean Tempmax of 19.6 ± 2.4 °C with relative humidity of 61 %. On heat-stress days, patients showed significantly greater symptoms (17.3 ± 1.8 vs. 10.5 ± 0.37 points) and fewer total steps/day than on thermal-comfort days (3,995 ± 2,013 vs. 5,567 ± 2,434 steps/day; both P \ 0.001, respectively) (Fig. 1a, b). In regard to the daily symptom score, the domains ‘‘impairment of daily activities,’’ ‘‘energy levels,’’ and ‘‘quality of sleep’’ especially were affected on heat-stress days compared to thermal-comfort days. There was a significant negative correlation between total steps/day, Tempmax (R = -0.47; P \ 0.001), and humidity (R = -0.34; P \ 0.001), as well as between daily symptoms and total steps/day (R = -0.67; P \ 0.001). A significant positive correlation was found between daily symptoms, Tempmax (R = ?0.79; P \ 0.001), and humidity (R = ?0.23; P \ 0.001). The product of humidity and Tempmax showed a stronger negative correlation with daily steps/day than either climate parameter on its own (R = -0.54; P \ 0.001) (Fig. 2a). Similarly, the product showed a strong positive correlation with daily symptoms score (R = ?0.72; P \ 0.001) (Fig. 2b). Day-to-day variation in activity levels and subjective symptoms in relation to outside temperature fluctuations can be seen in Fig. 3a, b.
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Fig. 1 Box plots showing a daily steps and b daily symptoms score on heat-stress days (Tempmax C 25 °C) compared to thermal comfort days (Tempmax \ 25 °C) in 15 PAH patients. Statistical significance is set at P \ 0.05
Fig. 2 Scatter plot showing the association of a daily steps and b daily symptoms score and temperature 9 humidity from April 1 to September 30 in 15 PAH patients
Strengths and Limitations Discussion Main Findings Heat stress is associated with worse symptoms and a reduction in physical activity levels in patients with PAH. By means of continuous monitoring we were able to investigate day-to-day variations in physical activity levels and symptoms in response to outside temperature and how the temperature affects health status in our patient cohort during episodes of summer heat waves. Heat stress places a significant strain on PAH patients by putting them at greater risk for morbidity such as heat stress-induced decompensation. Therefore, chronic disease management must adapt therapeutic measures to shield vulnerable patients from heat-stress exposure.
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The strength of this study lies in the use of continuous monitoring to obtain clinical status and functional performance data during both heat-stress and thermal-comfort days. The primary aim of the study was to evaluate the impact of urban heat stress on daily symptoms and activity levels in patients with PAH. We believe that extreme temperature changes associated with global warming will significantly impair the health of vulnerable patients with chronic diseases. Our data support existing knowledge by using PAH patients as an example. Limitations to this study include the small number of patients and the lack of a healthy control group in order to support our statement that patients with chronic diseases are disproportionately affected by heat stress compared to healthy people. Unfortunately, our resources were very limited in this small study.
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activity threshold defined as sedentary in healthy individuals [10, 23]. Moreover, heat stress further attenuates already limited physical activity levels and increases the feeling of discomfort by aggravating disease-specific symptoms in patients with PAH. We found that the daily step count was reduced by and perceived daily symptoms were increased by 30 %, respectively, on days with high temperature and humidity compared to thermal-comfort days. This implies that PAH patients lack the internal capacity to adapt and respond to heat stress. Therefore, external adaptive measures are needed such as adequate room cooling in the patient’s home and at the hospital in order to prevent heat stress-induced morbidity. Implications for Future Research According to a report from the Center for Health and the Global Environment at Harvard Medical School, there will be a dramatic increase in the number, duration, and intensity of extreme weather events, including heat waves [24]. There will be an increase in temperature variance leading to more record hot days and more record cold days. This has a significant implication for health status and wellbeing in patients with PAH and puts them at risk for heatrelated morbidity. Adaptation strategies must be in place to protect vulnerable patients at risk for heat stress-induced decompensation in order to reduce poor outcome. These strategies include, but are not limited to, continuous patient monitoring, indoor climate control, and proper adaptive behavior during and outside of heat stress, as well as necessary adjustments in pharmacological therapy. Fig. 3 Dual-axis box plots with the y axis depicting a daily steps and b daily symptoms score in 15 PAH patients. The x axis indicates the days from April 1 to September 30 and the z axis (black line) shows daily values for temperature 9 humidity
Implications and Findings in Relation to Previous Published Work Several studies have looked at the ramifications of heat stress on patients with other chronic diseases such as heart disease, diabetes, and COPD [1, 18–21]. This is the first study, however, that investigated the effects of heat stress on exercise capacity and clinical status in patients with PAH. We were able to show a significant reduction in exercise capacity and an increase in disease-specific symptoms on heat-stress days. Previous research has demonstrated that daily physical activity levels are significantly reduced in patients with PAH compared to age-matched healthy individuals, reflecting limited health-related quality of life [10, 22]. Similar to findings by Mainguy et al. [10], our patient cohort averaged 5,000 steps/day over the 6-month observation period, an
Conclusions Heat stress is significantly associated with a reduction in exercise capacity and an increase in disease-related symptoms. This, in turn, will make PAH patients more vulnerable for morbidity. These findings are preliminary and must be confirmed in a larger patient population. Acknowledgments This study was funded by the German Ministry for Education and Research (BMBF: NCT01LR0803L) and Deutsche Forschungsgemeinschaft (DFG), Research Unit 1736 Urban Climate Change and Heat Stress in mid-latitude cities in view of climate change (UCaHS) WI-1516/2-1. Conflict of interest The authors declare that they have no conflicts of interest in relation to this article.
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Heat Stress is Associated with Reduced Health Status in Pulmonary Arterial Hypertension: A Prospective Study Cohort Melissa Jehn • Andreas Gebhardt • Uta Liebers • Bahar Kiran • Dieter Scherer • Wilfried Endlicher Christian Witt
•
Received: 25 November 2013 / Accepted: 11 April 2014 Ó European Union 2014
Abstract 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 M. Jehn (&) A. Gebhardt U. Liebers B. Kiran C. Witt (&) Division of Pneumological Oncology and Transplantology, Charite´ Universita¨tsmedizin Berlin, Campus Charite´ Mitte, Charite´platz 1, 10117 Berlin, Germany e-mail: [email protected] C. Witt e-mail: [email protected] D. Scherer Institute for Ecology, Technische Universita¨t Berlin (on behalf of the UCaSH Research Group), Berlin, Germany W. Endlicher Geography Department, Humboldt-Universita¨t zu Berlin (on behalf of the KLIMZUG Research Group), Berlin, Germany
significant negative correlation between total steps/day and Tempmax (R = -0.47; P \ 0.001) and humidity (R = -0.34; P \ 0.001). A significant positive correlation was found between daily symptoms and Tempmax (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. Keywords Vulnerability Heat stress Exacerbation frequency Activity monitoring
Introduction With global warming, extreme temperature changes (both hot and cold) will become more frequent, and, in particular, heat waves will last longer and be more intense [1, 2]. How this will affect human health, especially that of patients with pulmonary arterial hypertension (PAH), is poorly understood at present. PAH is a rare lung disease characterized by reduced quality of life and overall poor patient outcome [3]. Epidemiological studies show an increase in morbidity and mortality on hot days among patients with respiratory diseases, including PAH [4–7]. Nevertheless, little is known about the clinical and functional consequences of heat stress in patients with PAH, in particular, the degree of physical impairment [6]. Exercise capacity is an integral component in the clinical evaluation of PAH patients, because the degree of physical impairment strongly correlates with clinical prognosis. Continuous ambulatory activity measured by an accelerometer is a surrogate marker of functional exercise
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capacity in patients with chronic diseases [8, 9]. The analysis of daily activity patterns over time, including the amount of sedentary time, enables clinicians to evaluate therapy more thoroughly [10]. The multidisciplinary German Federal Research Program KLIMZUG (‘‘Klima in Regionen zukunftsfa¨hig gestalten’’) aims to investigate adaptation strategies to climate change in Berlin, Germany, a metropolitan midlatitude area surrounded by the countryside of Brandenburg (trial registration: DRKS-ID: DRK00000705). One of the working goals of this project is to assess the degree of medical vulnerability of PAH patients susceptible to heat stress, including their clinical status, exercise capacity, and subsequent therapeutic measures. The primary aim of this study is to evaluate whether exposure to heat stress is associated with a reduction in functional capacity of patients with PAH measured by means of daily symptoms and accelerometer-based physical activity levels. Methods Fifteen clinically stable patients diagnosed with PAH were included in this study [11]. Clinical diagnosis of PAH was based of clinical history, physical examination, echocardiography, and right-sided heart catheterization, with mean pulmonary artery pressure [ 25 mmHg at rest and capillary wedge pressure \ 15 mmHg [12]. Inclusion criterion was New York Heart Association (NYHA) functional class II–IV. Exclusion criterion was having any malignant disease, particularly one that limits exercise tolerance such as chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), or rheumatoid arthritis. Patients were also excluded if they had any severe musculoskeletal disorders that prevented them from walking without assistance. Patients had an initial baseline examination and a follow-up exam at 6 months. Assessments included detailed medical history, duration of PAH, comorbidities, physical examination, spirometry, 6-minute walk test, NTproBNP, and systolic pulmonary artery pressure (sPAP). The Modified Medical Research Council (MMRC) Dyspnea Scale was assessed at baseline and then once a month for the 6 months of the study. Patients were categorized according to functional classes II– IV based on their level of exercise tolerance, with a higher functional class (FC) indicating greater disease severity. The study was carried out according to the principles of the Declaration of Helsinki and approved by our local ethics committee (Ethics No. EA1/033/10). Written informed consent was obtained from all participating patients.
to wear the device throughout the day from April 1 to September 30 while going about their daily business. The device was attached to the patient’s belt and positioned above the left hip. Patients were instructed to attach the device upon rising in the morning and to take it off only for showering, bathing, and sleeping. Activity data were recorded continuously (24 h) and the time when it was not worn was indicated as ‘‘resting mode.’’ All device settings were preprogrammed for each patient and the device was ‘‘on’’ throughout the entire measurement period to keep handling of the accelerometer by the patient to a minimum. The screen display was set to ‘‘standby’’ mode to hide data analysis. Therefore, patients did not receive any direct feedback from the device regarding their daily activity time, energy expenditure, distance, or number of steps taken. Upon return of the accelerometer, the data were downloaded onto a PC and viewed via the ActiCoach MPAT2Viewer program (Aipermon). Wearing time included min/day spent passively (i.e., sitting), actively (i.e., moving but not walking), walking (0–5 km/h or 0–80 m/min), and fast walking ([5 km/h or 81–115 m/min), steps, calories, and distance (m). The device used was a three-dimensional accelerometer that measures movement continuously in three axes (x, y, z). Data output is provided in 60-s intervals for each consecutive day (24 h), with the exact time and date for each epoch. Activity modes and accelerometer detection accuracy were extensively validated and detailed results are reported elsewhere [13]. In summary, the device was able to detect steps to 99 % accuracy at walking speeds as low as 20 m/min. The thresholds used to classify walking speeds are set by the manufacturer and based on the walking behavior of older individuals with heart failure [13, 14], a patient population for which it was originally designed using a large multicenter study that investigated the feasibility of remote patient telemonitoring [15–17]. Daily Symptoms Score The questions of the daily symptom score were adapted directly from the COPD Assessment Test (CAT). The questionnaire consisted of seven questions that were weighed on a scale of 0–5, with higher scores indicating worse symptoms. Question referred to (1) impairment in daily activities, (2) breathlessness going up stairs, (3) worries about leaving the house, (4) quality of sleep, (5) energy level, (6) occurrence of cyanosis related to lung disease, and (7) existence of edema. Scores given to individual questions were added up for a total score for each day, which was used for all subsequent analyses.
Accelerometer Activity Monitoring
Assessment of Temperature Data
Patients were given an accelerometer (Aipermon GmbH, Munich, Germany) during their baseline visit and instructed
Data regarding daily temperature (in °C) were obtained from the local weather station (Tempelhof, Berlin, Germany;
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maintained by the Deutscher Wetterdienst) and included daily temperature readings (Tempmean, Tempmax, Tempmin), air pressure (hPa), and humidity (%). This weather station is located 48 m above normal null (NN) at 52.47° N 13.4° E. Days when the Tempmax C 25 °C were considered ‘‘heatstress days,’’ whereas days when the Tempmax \ 25 °C were regarded as ‘‘thermal-comfort days.’’ To combine temperature and humidity, the following formula was applied: temperature 9 humidity (%) /100. Statistical Analysis Statistical analysis was performed using SPSS software ver. 21.0 (SPSS Inc., Chicago, IL, USA). Data were descriptively analyzed and reported as mean ± standard deviation (SD) for quantitative measurements and percentages for frequencies. Bivariate correlations of nonparametric variables were investigated using Spearman-Rho correlation coefficient (R). Differences between heat-stress and thermalcomfort days were compared using a paired Student’s t test for normally distributed variables. P values less than 0.05 were considered statistically significant. Scatter plots were used to illustrate the association of temperature and humidity with daily activity levels and symptoms score. Box plots and bar graphs were used to illustrate the influence of daily climate data on clinical parameters, including daily activity levels and symptoms score.
Results Patient Characteristics Baseline patient characteristics are given in Table 1. Mean changes from the baseline parameters to 6-month follow-up were ?13.2 ± 64.6 m in 6-min walk test distance, ?32.4 ± 775 pg/ml in NTproBNP, ?2.8 ± 10.73 mmHg in sPAP, -0.1 ± 1.02 in the MMRC Dyspnea Scale, and ?2.2 ± 1.78 % in FEV1 (%). Patients walked an average of 4,998 ± 2,229 steps/day and had a symptom score of 14.6 ± 7.2 points over the 6-month monitoring period. Total steps per day showed a significant positive correlation with the 6-min walking distance at baseline and at the 6-month follow-up (R = ?0.79 and ?0.71, respectively; P \ 0.001). Finally, change in mean pulmonary arterial pressure was significantly associated with changes in NTproBNP levels, both at baseline and the 6-month follow-up (R = ?0.79 and ?0.88, respectively; P \ 0.001). Monitoring Period (April 1–September 30, 2011) Between April 1 and September 30, 2011, there were 65 heatstress days and 118 thermal-comfort days. On heat-stress
Table 1 Patient characteristics at baseline N
15
Gender (male/female)
9/6
Age (years)
63.5
BMI (kg/m2)
28.9 ± 14.8
FEV1 (%)
61.7 ± 19.1
NYHA functional class
NYHA II = 5 NYHA III = 10
MMRC
3.5 ± 1.08
sPAP (mmHg)
65.8 ± 14.5
NTproBNP (pg/ml)
1016 ± 1131
6MWT (m)
287 ± 93.7
SpO2 saturation during 6MWT
86.0 ± 2.8
HR during 6MWT
112.2 ± 8.9
Medication Oral anticoagulation Iloprost
10 (67 %) 6 (40 %)
Phosphodiesterase-5 inhibitor
8 (53 %)
Endothelin receptor antagonist
12 (80 %)
Long term O2 therapy
15 (100 %)
Data are presented as mean ± SD and frequencies (%) 6MWT 6-minute walk test, sPAP systolic pulmonary artery pressure, MMRC Modified Medical Research Council, BMI body mass index, FEV1 forced expiratory volume in 1 second, NYHA New York Heart Association functional class, SpO2 oxygen saturation
days, the temperature according to the German Weather Service reached an average Tempmax of 27.0 ± 2.0 °C with relative humidity of 66 %. Thermal-comfort days had a mean Tempmax of 19.6 ± 2.4 °C with relative humidity of 61 %. On heat-stress days, patients showed significantly greater symptoms (17.3 ± 1.8 vs. 10.5 ± 0.37 points) and fewer total steps/day than on thermal-comfort days (3,995 ± 2,013 vs. 5,567 ± 2,434 steps/day; both P \ 0.001, respectively) (Fig. 1a, b). In regard to the daily symptom score, the domains ‘‘impairment of daily activities,’’ ‘‘energy levels,’’ and ‘‘quality of sleep’’ especially were affected on heat-stress days compared to thermal-comfort days. There was a significant negative correlation between total steps/day, Tempmax (R = -0.47; P \ 0.001), and humidity (R = -0.34; P \ 0.001), as well as between daily symptoms and total steps/day (R = -0.67; P \ 0.001). A significant positive correlation was found between daily symptoms, Tempmax (R = ?0.79; P \ 0.001), and humidity (R = ?0.23; P \ 0.001). The product of humidity and Tempmax showed a stronger negative correlation with daily steps/day than either climate parameter on its own (R = -0.54; P \ 0.001) (Fig. 2a). Similarly, the product showed a strong positive correlation with daily symptoms score (R = ?0.72; P \ 0.001) (Fig. 2b). Day-to-day variation in activity levels and subjective symptoms in relation to outside temperature fluctuations can be seen in Fig. 3a, b.
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Fig. 1 Box plots showing a daily steps and b daily symptoms score on heat-stress days (Tempmax C 25 °C) compared to thermal comfort days (Tempmax \ 25 °C) in 15 PAH patients. Statistical significance is set at P \ 0.05
Fig. 2 Scatter plot showing the association of a daily steps and b daily symptoms score and temperature 9 humidity from April 1 to September 30 in 15 PAH patients
Strengths and Limitations Discussion Main Findings Heat stress is associated with worse symptoms and a reduction in physical activity levels in patients with PAH. By means of continuous monitoring we were able to investigate day-to-day variations in physical activity levels and symptoms in response to outside temperature and how the temperature affects health status in our patient cohort during episodes of summer heat waves. Heat stress places a significant strain on PAH patients by putting them at greater risk for morbidity such as heat stress-induced decompensation. Therefore, chronic disease management must adapt therapeutic measures to shield vulnerable patients from heat-stress exposure.
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The strength of this study lies in the use of continuous monitoring to obtain clinical status and functional performance data during both heat-stress and thermal-comfort days. The primary aim of the study was to evaluate the impact of urban heat stress on daily symptoms and activity levels in patients with PAH. We believe that extreme temperature changes associated with global warming will significantly impair the health of vulnerable patients with chronic diseases. Our data support existing knowledge by using PAH patients as an example. Limitations to this study include the small number of patients and the lack of a healthy control group in order to support our statement that patients with chronic diseases are disproportionately affected by heat stress compared to healthy people. Unfortunately, our resources were very limited in this small study.
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activity threshold defined as sedentary in healthy individuals [10, 23]. Moreover, heat stress further attenuates already limited physical activity levels and increases the feeling of discomfort by aggravating disease-specific symptoms in patients with PAH. We found that the daily step count was reduced by and perceived daily symptoms were increased by 30 %, respectively, on days with high temperature and humidity compared to thermal-comfort days. This implies that PAH patients lack the internal capacity to adapt and respond to heat stress. Therefore, external adaptive measures are needed such as adequate room cooling in the patient’s home and at the hospital in order to prevent heat stress-induced morbidity. Implications for Future Research According to a report from the Center for Health and the Global Environment at Harvard Medical School, there will be a dramatic increase in the number, duration, and intensity of extreme weather events, including heat waves [24]. There will be an increase in temperature variance leading to more record hot days and more record cold days. This has a significant implication for health status and wellbeing in patients with PAH and puts them at risk for heatrelated morbidity. Adaptation strategies must be in place to protect vulnerable patients at risk for heat stress-induced decompensation in order to reduce poor outcome. These strategies include, but are not limited to, continuous patient monitoring, indoor climate control, and proper adaptive behavior during and outside of heat stress, as well as necessary adjustments in pharmacological therapy. Fig. 3 Dual-axis box plots with the y axis depicting a daily steps and b daily symptoms score in 15 PAH patients. The x axis indicates the days from April 1 to September 30 and the z axis (black line) shows daily values for temperature 9 humidity
Implications and Findings in Relation to Previous Published Work Several studies have looked at the ramifications of heat stress on patients with other chronic diseases such as heart disease, diabetes, and COPD [1, 18–21]. This is the first study, however, that investigated the effects of heat stress on exercise capacity and clinical status in patients with PAH. We were able to show a significant reduction in exercise capacity and an increase in disease-specific symptoms on heat-stress days. Previous research has demonstrated that daily physical activity levels are significantly reduced in patients with PAH compared to age-matched healthy individuals, reflecting limited health-related quality of life [10, 22]. Similar to findings by Mainguy et al. [10], our patient cohort averaged 5,000 steps/day over the 6-month observation period, an
Conclusions Heat stress is significantly associated with a reduction in exercise capacity and an increase in disease-related symptoms. This, in turn, will make PAH patients more vulnerable for morbidity. These findings are preliminary and must be confirmed in a larger patient population. Acknowledgments This study was funded by the German Ministry for Education and Research (BMBF: NCT01LR0803L) and Deutsche Forschungsgemeinschaft (DFG), Research Unit 1736 Urban Climate Change and Heat Stress in mid-latitude cities in view of climate change (UCaHS) WI-1516/2-1. Conflict of interest The authors declare that they have no conflicts of interest in relation to this article.
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