Cell Biochem Biophys (2015) 71:789–794 DOI 10.1007/s12013-014-0264-2
ORIGINAL PAPER
Cardiopulmonary Exercise Capacity and Ventilation Effectiveness in Patients after Clinical Cure of Acute Irritant Gas Poisoning Rong Yan • Wenlan Yang • Jinming Liu • Beilan Gao • Kongrong Guo • Daoyuan Sun
Published online: 6 December 2014 Ó Springer Science+Business Media New York 2014
Abstract The aim of this study is to assess the medium to long-term effect of acute irritant gas poisoning on cardiopulmonary exercise function in patients after clinical cure. Fourteen patients after an average of 18.5 months of clinical cure of acute irritant gas poisoning were recruited, and 14 healthy individuals were selected as control. All subjects were examined by resting pulmonary function testing (RPFT), cardiopulmonary exercise testing (CPET), and arterial blood gas (ABG) analysis. No statistically significant differences were found between poisoning and control groups for baseline parameters (age, height, and weight) or ABG values (pH, PaO2, PaCO2, and SaO2) (P [ 0.05). For most RPFT parameters, including FEV1/FVC, FEV1, FEV1%pred, RV/TLC, DLCO%, and FVC%, no statistically significant differences were observed between
poisoning and control groups (P [ 0.05). However, MVV% was significantly lower in poisoning group compared with healthy individuals (P \ 0.05). Statistically significant differences were observed for some CPET parameters, including peak VO2, peak VO2/kg, peak VE, and lowest VE/VCO2 (P \ 0.05), and peak load, VD/VT, and peak PETCO2 (P \ 0.01) between the two groups. However, there were no statistically significant differences in peak VO2%pred or peak O2 pulse between poisoning and control groups (P [ 0.05). Compared with controls, patients with acute irritant gas poisoning had decreased cardiopulmonary exercise capacity and ventilation effectiveness after clinical cure. Keywords Acute poisoning Irritant gas Cardiopulmonary exercise testing Ventilation effectiveness
Rong Yan and Wenlan Yang contributed equally to this study. R. Yan K. Guo Department of Occupational Poisoning, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China W. Yang Pulmonary Function Test Room, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China J. Liu (&) Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China e-mail: [email protected] B. Gao (&) D. Sun Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China e-mail: [email protected]
Introduction Irritant gases such as ammonia, nitrogen oxides, nitric acid, and hydrogen sulfide, when exposed to human body, can cause eye irritation or chemical eye burns [1], allergic contact dermatitis [2], and more seriously, the airway injury [3]. Acute exposure to high concentrations of toxic gas over a short time is characteristic of industrial accident, which poses as a global issue in certain professional lines [4]. Mild cases of irritant gas injury are manifested as respiratory inflammation, whereas severe cases are associated with toxic pulmonary edema or even acute respiratory distress syndrome (ARDS), potentially causing death. According to a report on acute occupational poisoning in China, irritant gas poisoning accounts for a large proportion of occupational poisoning [4, 5]. During 1989–2003,
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92 irritant gas poisoning accidents with a total of 1,330 cases and 72 deaths were reported in 23 provinces, autonomous regions, and municipalities in China; the annual average number of irritant gas poisoning accidents was 6.1, accounting for 18 % of the nation’s average number of poisoning accidents in the same period; the annual average number of irritant gas poisoning cases of 88.7 with 4.8 deaths, accounting for 5.4 % of total poisoning mortality rates [5]. Fortunately, if treated timely and correctly, poisoning symptoms in patients with toxic pulmonary edema can be controlled in 2–3 days, the associated X-ray changes disappear in approximately 1 week, and most the patients can recovery fully, although interstitial fibrosis may persist in specific cases. Despite of the high significance, few follow-up studies have been reported on the cardiopulmonary function in patients after clinical cure of acute irritant gas poisoning. Therefore, we aimed in this study to investigate cardiopulmonary exercise function in patients after clinical treatment of acute irritant gas poisoning, to assess the medium to long-term effect of acute irritant gas poison on human health. We used the cardiopulmonary exercise testing (CPET) as the main detecting measure for objective evaluation of cardiopulmonary functional reserve and exercise tolerance. Moreover, routine pulmonary function testing (RPFT) and arterial blood gas (ABG) analysis were also applied, and the results were compared with those collected from healthy individuals, in order to examine the impact of irritant gas poisoning on exercise tolerance and ventilation effectiveness.
Methods Patient Selection In this prospective cohort study, 14 patients with acute irritant gas poisoning (poisoning group) were selected from the intoxication department of our hospital from February 2009 to December 2012. The patients were males, 33–64 years old (average, 50.21 ± 7.96), 164.86 ± 4.06 cm in height, and 67.07 ± 5.23 kg in weight. Diagnosis and grading of patients were based on GBZ 73-2009 Diagnostic Criteria of occupational acute toxic respiratory system disease [6]. The patients included 10 cases of severe poisoning and 4 cases of moderate poisoning, respectively. All 14 cases had acute toxic pulmonary edema caused by exposure to irritant gases, including toxic nitrogen oxides, nitric acid, and hydrogen sulfide. The patients were admitted into the hospital several hours to 2 days after exposure to the above-mentioned irritants. Clinical cure was achieved by hormone administration, oxygen therapy,
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infection prevention, antioxidant treatment, stomach protection, and supporting therapy. The patients were clinically examined at follow-up appointments during 4–24 months, in average 18.5 months. Chest computed tomography (CT) scan showed that the original oozing lesions in both lungs were absorbed in cured patients; small cord-like shadows persisted in 2 patients only; and diffuse, tiny miliary nodules were found in one patient despite the obvious absorption of primary lesion. The exclusion criteria comprised respiratory diseases before the poisoning accident and pre-existing severe diseases of muscle and cardiovascular, nervous, and endocrine systems. The control group included 14 healthy male volunteers, matched for gender, age, height, and body weight with patients group. Inclusion criteria were no obvious heart, lung, bone, joint, muscle, nerve, or endocrine system disease. The study protocols were reviewed and approved by the ethics committee of our hospital and all subjects provided signed informed consent. RPFT Procedure RPFT was conducted at follow-up appointments using a Master Screen Diffusion modular spirometer (Jaeger, Germany). After rigorous calibration of the equipment, acceptable RPFT was completed in each subject at least three times at 1 min interval. The detection error was \5 % and the best values of detection parameters were recorded. RPFT parameters included forced expiratory volume in one second/forced vital capacity (FEV1/FVC), forced expiratory volume in one second (FEV1), percentage of forced expiratory volume in the first second in the predicted value (FEV1%pred), ratio of residual volume to total lung capacity (RV/TLC), diffusion capacity for carbon monoxide of lung (DLCO%), percentage of forced vital capacity in the predicted value (FVC%pred), and maximal voluntary ventilation% (MVV%pred). The formula of RPFT predicted value used in this study referred to that of normal predicted value of lung function in Chinese adults, as established in 1988. CPET Procedure CPET was carried out using a Master Screen-CPX test system (Jaeger, German). The flow sensor and gas analyzer were calibrated before use. A ramp-incremental symptomlimited CPET test was conducted by selecting different loads (10–25 W/min) according to the disease situation of patients, pulmonary function and the related preset programs, providing 8–12 min of exercise time. During the entire CPET test, dynamic monitoring was carried out on 12-lead electrocardiogram (ECG) for blood pressure, pulse oxygen saturation, and pulmonary ventilation. Raw data of
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gas (CO2 and O2) exchange were recorded using the breathby-breath method, and the anaerobic threshold was determined using the V-slope method [7]. The mean data for every 10 s interval were used for various graphing and subsequent calculations [8–10]. The CPET test was suspended in the following cases: (1) ECG indicates ST-segment depression of 2 mm accompanied by chest pain or STsegment depression of 3 mm without chest pain, frequent premature ventricular beat, and second- and third-degree atrioventricular block; (2) systolic blood pressure C 250 mmHg and/or diastolic blood pressure C 120 mmHg, and decrease in blood pressure relative to baseline blood pressure C 30 mmHg; and (3) pulse oxygen saturation B 80 %. Most subjects were willing to end the test due to leg pain, exhaustion, or breathing difficulties. The following parameters were read and recorded: peak load, peak O2 uptake (peak VO2), percentage of peak VO2 in the predicted value (peak VO2%pred), peak VO2 per kilogram (peak VO2/kg), peak ventilatory capacity (peak VE), peak O2 pulse, lowest ventilatory equivalent of CO2 (lowest VE/VCO2), physiologic dead space/tidal volume (VD/VT), and peak end-tidal CO2 partial pressure (peak PETCO2). The formula of CPET predicted value referred to the CPET guidelines issued by the American Thoracic Society/ American College of Chest Physicians (ATS/ACCP) in 2003 [11]. ABG Analysis On the same day of RPFT and CPET, arterial blood was drawn from radial artery of the forearm for each subject. Blood samples were analyzed using an automatic blood gas analyzer (Radiometer ABL800, Denmark). Arterial blood pH, oxygen partial pressure, CO2 partial pressure, and oxygen saturation values were read and recorded. Statistical Analysis Data analysis was conducted using the Statistical Package for the Social Sciences 13.0 (SPSS, Chicago, IL, USA). All data are presented as mean ± standard deviation. The values obtained for each parameter were compared between groups by the independent sample t test. P \ 0.05 was considered statistically significant, and P \ 0.01 was considered highly statistically significant.
Results Baseline Characteristics and ABG Data of the Poisoning and Control Groups In this study, both poisoning and control groups comprised 14 males. The patients in the poisoning group and control
791 Table 1 Baseline characteristics and partial results of blood gas analysis in poisoning and control groups (mean ± standard deviation) Variable
Poisoning group
Control group
Individuals
14
14
P value
Age (year)
50.21 ± 7.96
50.50 ± 2.50
[0.05
Height (cm)
164.86 ± 4.06
165.43 ± 2.41
[0.05
Weight (kg)
67.07 ± 5.23
66.93 ± 8.50
[0.05
pH
7.45 ± 0.18
7.44 ± 0.12
[0.05
PaO2 (mmHg) PaCO2 (mmHg)
90.36 ± 6.22 37.31 ± 4.14
91.74 ± 5.24 38.39 ± 3.06
[0.05 [0.05
SaO2 (%)
97.19 ± 0.66
96.96 ± 0.63
[0.05
Blood gas analysis
individuals were 50.21 ± 7.96 and 50.50 ± 2.50 years old, respectively. In the poisoning group, patients were 164.86 ± 4.06 cm tall and weighed 67.07 ± 5.23 kg, whereas height and weights of control individuals were 165.43 ± 2.41 cm and 66.93 ± 8.50 kg, respectively, as shown in Table 1. These data were comparable between the two groups, with no statistically significant differences in terms of age, height, or weight (P [ 0.05). ABG parameters were not altered in the poisoning group, including PaO2 (90.36 ± 6.22 vs. 91.74 ± 5.24 mmHg for controls, P [ 0.05), PaCO2 (37.31 ± 4.14 vs. 38.39 ± 3.06 mmHg for healthy individuals, P [ 0.05), and SaO2 (97.19 ± 0.66 vs. 96.96 ± 0.63 % for controls, P [ 0.05), all within normal ranges. These data demonstrated that no obvious hypoxemia, CO2 retention, or acid–base imbalance was present in either group (Table 1). Effective Treatment of Patients with Acute Irritant Gas Poisoning In the poisoning group, clinical symptoms such as cough, chest tightness, and shortness of breath were generally eliminated in the 14 patients after active treatment. Additionally, the positive signs and dry/wet rales of lung disappeared and the results of imaging tests (chest radiograph and chest CT) were significantly improved, complying with the clinical cure criteria. PFT Data of the Poisoning and Control Groups PFT data were comparable for most parameters in poisoning and control groups with, respectively, 78.53 ± 4.89 and 79.71 ± 5.35 % (FEV1/FVC), 93.64 ± 12.23 and 98.71 ± 8.94 % (FEV1%pred), 2.76 ± 0.46 and 3.01 ± 0.38 L (FEV1), 98.93 ± 12.65 and 103.39 ± 10.86 % (FVC), 35.36 ± 5.98 and 33.30 ± 1.37 % (RV/TLC), and 106.95 ± 24.31 and 116.26 ± 16.57 % (DLCO), showing no significant differences (P [ 0.05). These data indicated
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Table 2 Pulmonary function data in poisoning and control groups (mean ± standard deviation)
CPET Data of the Poisoning and Control Groups
Variable
We found that peak VO2, peak VO2/kg, and peak VE were lower in the poisoning group with 1567.07 ± 452.40, 23.33 ± 7.29, and 52.14 ± 16.68, respectively, compared with 1881.58 ± 328.67, 28.12 ± 3.61, and 67.83 ± 12.73, respectively, observed in healthy individuals (P \ 0.05) as shown in Table 3. In the poisoning group, peak load (108.64 ± 35.91) and peak PETCO2 (34.07 ± 7.10) were highly significantly lower than in the control group (151.43 ± 23.94 and 40.88 ± 2.04 for Peak load and PETCO2, respectively) at P \ 0.01 (Table 3). In contrast, VD/VT was markedly higher in the poisoning group (31.64 ± 5.06) than in the control group (24.76 ± 3.48), showing highly statistically significant differences (P \ 0.01). Likewise, the lowest VE/VCO2 was higher in the poisoning group than in the control group with 30.61 ± 5.23 and 27.34 ± 0.73, respectively, a statistically significant differences (P \ 0.05); there were no statistically significant differences in the peak VO2%pred (72.50 ± 19.73 vs. 81.91 ± 9.98) and peak O2 pulse (12.13 ± 1.86 vs. 12.53 ± 0.92) between the two groups (P [ 0.05) as shown in Table 3.
Poisoning group
Control group
P value [0.05
FEV1/FVC (%)
78.53 ± 4.89
79.71 ± 5.35
FEV1%pred (%)
93.64 ± 12.23
98.71 ± 8.94
[0.05
2.76 ± 0.46
3.01 ± 0.38
[0.05 [0.05
FEV1 (L) FVC%
98.93 ± 12.65
103.39 ± 10.86
MVV%pred
91.66 ± 20.24
106.28 ± 17.08*
\0.05
RV/TLC (%)
35.36 ± 5.98
33.30 ± 1.37
[0.05
106.95 ± 24.31
116.26 ± 16.57
[0.05
DLCO%
* Compare to the control group, p \ 0.05 FEV1/FVC forced expiratory volume in one second/forced vital capacity, FEV1%pred percentage of forced expiratory volume in the first second in the predicted value, MVV%pred maximal voluntary ventilation%, RV/TLC ratio of residual volume to total lung capacity, DLCO% diffusion capacity for carbon monoxide of lung, FVC% percentage of forced vital capacity
Table 3 Cardiopulmonary exercise data in poisoning and control groups (mean ± standard deviation) Variable
Poisoning group
Control group
P value
Peak load (W)
108.64 ± 35.91
151.43 ± 23.94** \0.01
Peak VO2 (mL/ min)
1567.07 ± 452.40
1881.58 ± 328.67* \0.05
Peak VO2%pred
72.50 ± 19.73
81.91 ± 9.98
[0.05
Discussion
Peak VO2/kg (mL/min/kg)
23.33 ± 7.29
28.12 ± 3.61*
\0.05
Peak VE (L/ min)
52.14 ± 16.68
67.83 ± 12.73*
\0.05
Peak PETCO2 (mmHg)
34.07 ± 7.10
40.88 ± 2.04**
\0.01
Peak O2 pulse (mL/beat)
12.13 ± 1.86
12.53 ± 0.92
[0.05
Lowest VE/ VCO2
30.61 ± 5.23
27.34 ± 0.73*
\0.05
VD/VT (%)
31.64 ± 5.06
24.76 ± 3.48**
\0.01
Irritant gases cause health ailments at various sites of the body, including eyes, skin, and lungs [5]. This is a global issue as evidenced by respiratory risks linked to industrial environment and work conditions in certain professions [7]. The effects of such irritants are poorly understood, especially after treatment. Therefore, this study aimed to assess the cardiopulmonary function in patients after clinical treatment of acute irritant gas poisoning. The data demonstrated that patients cured from poisoning had decreased cardiopulmonary exercise capacity and ventilation effectiveness. Among the respiratory diseases related to irritant gas inhalation, toxic pulmonary edema and ARDS are two most severe complications that lead to loss of the labor force. Although a small number of studies have investigated pulmonary function in patients with irritant gas poisoning in China, their follow-up periods are relatively short. Zhou et al. [12] studied the changes in pulmonary function in 36 patients after clinical cure of acute irritant gas poisoning and found that pulmonary function was significantly recovered post treatment. Fu et al. reported 15 cases of acute toxic pulmonary edema related to irritant gas poisoning, of which 4 cases of ARDS retained pulmonary fibrosis and mainly showed pulmonary ventilation hypofunction. In the present study, data were collected from 14 patients after clinical cure of acute pulmonary edema related to
* Compare to the control group, p \ 0.05 ** Compare to the control group, p \ 0.01 Peak VO2 peak O2 uptake, peak VO2%pred percentage of peak VO2 in the predicted value, peak VO2/kg peak VO2 per kilogram, peak VE peak ventilatory capacity, lowest VE/VCO2 lowest ventilatory equivalent of CO2, VD/VT physiologic dead space/tidal volume, peak PETCO2 peak end-tidal CO2 partial pressure
that the poisoning group showed no obvious differences in pulmonary function, residual volume, and diffusion function, compared with the control group. An exception was that MVV% which was significantly lower in the poisoning group (91.66 ± 20.24 %) than in healthy individuals (106.28 ± 17.08 %, P \ 0.05), although remaining within the normal range (above 80 %) (Table 2).
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irritant gas poisoning (poisoning group), and then compared the values with those of 14 healthy volunteers (control group). The interaction of age, gender, height, and weight was excluded by matching the controls. Our data showed no significant differences in the major ABG or RPFT parameters between the poisoning and control groups. Interestingly, the major ABG parameters, including PaO2, PaCO2, and pH, were within normal ranges in the poisoning group. As for the RPFT data, the major parameters for pulmonary ventilation function, residual volume, and diffusion function were slightly lower in the poisoning group than in the control group, but the differences were not statistically significant. However, in the CPET data, statistically significant differences were found in the parameters for cardiopulmonary exercise capacity and ventilation effectiveness between the poisoning and control groups, probably pointing at some residual damage not seen on CT scans. In addition, we found that peak load, peak VO2, and peak VO2/kg were lower in the poisoning group compared with the control group, suggesting that cured patients with acute irritant gas poisoning had decreased exercise tolerance. Peak load is an important parameter that reflects exercise tolerance. The poisoning group showed significantly lower peak load than controls, indicating that the cured patients could support significantly lower loads than healthy individuals during exercise. Similarly, peak VO2 and peak VO2%pred are indicators for cardiopulmonary O2 uptake of individuals at maximal exercise, and are considered gold standard for evaluating exercise tolerance [11]. Our data showed lower peak VO2 values for the poisoning group compared with controls. Although slightly lower in the poisoning group than in the control group, the peak VO2%pred was not statistically different between the two groups. Together, these results demonstrate that the patients with acute irritant gas poisoning had obviously decreased O2 uptake efficiency and exercise tolerance during aerobic exercise, compared with healthy individuals. Compared with healthy individuals, cured patients in the poisoning group had increased lowest VE/VCO2 and VD/VT with decreased peak PET CO2. Lowest VE/VCO2, VD/VT, and peak PET CO2 are indicators for ventilation effectiveness. After inhalation of irritant gases, the chemicals can directly injure respiratory tract mucosa, damage alveolar structure, and affect gas exchange, thereby causing ventilation/perfusion imbalance and increasing the physiological dead space and VD/VT, eventually leading to increase in VE/VCO2. VD/VT is an indicator for evaluating the degree of ventilation/perfusion imbalance. In normal circumstances, the volume of resting physiological dead space is approximately 1/3 that of tidal volume; during exercise, the physiological dead space declines to approximately 1/5 that of tidal volume [13]. In patients with ventilatory defect, uneven ventilation causes ventilation/
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perfusion imbalance, accounting for the relatively high VD/ VT, especially during exercise [14]. In the present study, VD/VT was higher in the poisoning group than in the control group, indicating that ventilation/perfusion imbalance persisted to a certain degree in patients after clinical cure of acute irritant gas poisoning, leading to ineffective ventilation. The resulting decline of ventilatory efficiency and impediment of CO2 discharge resulted in increase in PaCO2 and lowest VE/VCO2, and decrease in peak PET CO2. Regarding the cardiopulmonary exercise function, the 14 cured patients with acute poisoning had normal resting pulmonary function but decreased exercise tolerance and ventilation effectiveness compared with healthy individuals. A possible mechanism that causes the above changes is that inhaled irritant gas causes direct injuries to the airway, alveolar epithelial cells and capillary endothelial cells, alveolar wall, and alveolar septa, thereby damaging the lung tissue structure. In the repair process of lung injury, airway and alveolar epithelial cells form fibrosis in the lesion. Then, the stimulated endothelial cells release collagenase, in order to degrade and alter collagen on the basilar membrane. Finally, cell proliferation and collagen synthesis are promoted by the chemotaxis of cytokines and inflammatory mediators. Although the results of imaging tests and resting pulmonary function had no significant changes, the CPET data demonstrated certain damage to the cardiopulmonary exercise function. It is inferred that the fine structure of lung tissues alters after acute irritant gas poisoning, thereby affecting the cardiopulmonary exercise function. It is not known wether the decline observed in pulmonary function changes is reversible or not [15]. However, it was shown that asthma in cleaning workers is characterized by non-reversible lung function decrement [16]. The RPFT and ABG data showed no significant differences between the cured patients and healthy individuals. However, multiple CPET parameters were found at abnormal levels in the cured patients. At this point, even mild impairment of the ventilatory mechanism could cause breathing difficulties during exercise. The injury that RPFT failed to detect was reflected by the CPET parameters. Together these results indicate that CPET is more effective than other examination methods for detecting physiological changes in the respiratory system after irritant gas poisoning; it allows more accurate and detailed measurement of the exercise capacity, and has higher sensitivity and greater potential advantages in evaluating the exercise capacity and injuries in patients with irritant gas poisoning. In patients treated with combination of mediastinal radiotherapy (RT) and polychemotherapy (CT) regimens, lower exercise capacity seems to be due to a combination of decreased cardiac performance and an impairment of gas diffusion capacity [17]. Many studies have emphasized the
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value of combined CPET parameters for determining lung injury [18–22]; evaluation of the injury with the RPFT parameters has limitations [14]. The importance of CPET for the assessment of occupational disease-related functional loss was shown in people exposed to or formally affected by irritant toxic, allergenic or fibrosing dusts, gases, welding fumes, and mineral fibers [23]. One of the main limitations of this work is the low number of individuals per group, which does not allow high statistical power and generalization. Therefore, larger cohorts should be studied in order to verify these findings. In addition, the healthy individuals could not be tested during the study for changes in their respiratory tract. In summary, the exercise tolerance and ventilation effectiveness decreased in patients after clinical cure of acute irritant gas poisoning. Presently, only RPFT parameters are generally used for assessing the labor capacity of patients with occupational toxic respiratory diseases. It is worthy further investigating and researching the application of CPET parameters in such assessments. Conflict of interest
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The authors declare no conflicts of interest. 16.
References 17. 1. Cordes, A. K., Frentz, M., & Schrage, N. F. (2011). Eye irritation and chemical eye burns. Review of experimental and clinical studies. Ophthalmologe, 108(10), 910–915. doi:10.1007/s00347010-2249-x. 2. Nettis, E., Colanardi, M. C., Soccio, A. L., Ferrannini, A., & Tursi, A. (2002). Occupational irritant and allergic contact dermatitis among healthcare workers. Contact Dermatitis, 46(2), 101–107. 3. Sahu, S., Roy, B., & Moitra, S. (2013). Assessment of the lung function status of the goldsmiths working in an unorganized sector of India. Lung India, 30(1), 33–37. doi:10.4103/09702113.106131. 4. Lin, Q. H., Liu, Y. M., & Guo, J. Y. (2012). Epidemiological study of occupational diseases in Guangzhou City, China in 2001–2010. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 30(10), 759–762. 5. Du, X. Y., Zhang, M., Wang, H. Q., Li, T., Wang, H. F., Chen, S. Y., et al. (2006). Characterization of severe acute occupational poisoning accidents related to irritating gases in China between 1989 and 2003. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 24(12), 716–719. 6. Diagnostic Criteria of occupational acute toxic respiratory system disease: People’s Medical Publishing House, 2009. 7. Beaver, W. L., Wasserman, K., & Whipp, B. J. (1986). A new method for detecting anaerobic threshold by gas exchange. Journal of Applied Physiology (1985)., 60(6), 2020–2027. 8. Sun, X. G., Hansen, J. E., Beshai, J. F., & Wasserman, K. (2010). Oscillatory breathing and exercise gas exchange abnormalities
123
18.
19.
20.
21.
22.
23.
prognosticate early mortality and morbidity in heart failure. Journal of the American College of Cardiology, 55(17), 1814–1823. doi:10.1016/j.jacc.2009.10.075. Sun, X. G., Hansen, J. E., Oudiz, R. J., & Wasserman, K. (2001). Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation, 104(4), 429–435. Sun, X. G., Hansen, J. E., Garatachea, N., Storer, T. W., & Wasserman, K. (2002). Ventilatory efficiency during exercise in healthy subjects. American Journal of Respiratory and Critical Care Medicine, 166(11), 1443–1448. doi:10.1164/rccm.2202033. American Thoracic Society. (2003). ATS/ACCP Statement on cardiopulmonary exercise testing. American Journal of Respiratory and Critical Care Medicine, 167(2), 211–277. doi:10.1164/ rccm.167.2.211. Zhou, P., Li, W. P., & Wang, H. S. (2006). Pulmonary function changes before and after treatment in patients with acute intoxication from stimulant gases. Clinical Medical Journal of China, 13, 580. Wasserman, K., Van Kessel, A. L., & Burton, G. G. (1967). Interaction of physiological mechanisms during exercise. Journal of Applied Physiology, 22(1), 71–85. Karlman W, James E, Darry lY (2008). Principles of exercise testing and interpretation-including pathophysiology and clinical applications. Forth ed. Philadelphia: Lippincott Williams & Wilkinks. Vizcaya, D., Mirabelli, M. C., Orriols, R., Anto, J. M., Barreiro, E., Burgos, F., et al. (2013). Functional and biological characteristics of asthma in cleaning workers. Respiratory Medicine, 107(5), 673–683. doi:10.1016/j.rmed.2013.01.011. Rothman, N., Ford, D. P., Baser, M. E., Hansen, J. A., O’Toole, T., Tockman, M. S., et al. (1991). Pulmonary function and respiratory symptoms in wildland firefighters. Journal of Occupational and Environmental Medicine, 33(11), 1163–1167. Villani, F., Busia, A., Villani, M., Laffranchi, A., Viviani, S., & Bonfante, V. (2009). Cardiopulmonary response to exercise in patients with different degrees of lung toxicity after radio-chemotherapy for Hodgkin’s disease. Anticancer Research, 29(2), 777–783. Cotes, J. E., Zejda, J., & King, B. (1988). Lung function impairment as a guide to exercise limitation in work-related lung disorders. American Review of Respiratory Disease, 137(5), 1089–1093. doi:10.1164/ajrccm/137.5.1089. Agostoni, P., Smith, D. D., Schoene, R. B., Robertson, H. T., & Butler, J. (1987). Evaluation of breathlessness in asbestos workers. Results of exercise testing. American Review of Respiratory Disease, 135(4), 812–816. Agusti, A., Roca, J., Rodriguez-Roisin, R., Xaubet, A., & AgustiVidal, A. (1988). Different patterns of gas exchange response to exercise in asbestosis and idiopathic pulmonary fibrosis. European Respiratory Journal, 1(6), 510–516. Howard, J., Mohsenifar, Z., Brown, H. V., & Koerner, S. K. (1982). Role of exercise testing in assessing functional respiratory impairment due to asbestos exposure. Journal of Occupational and Environmental Medicine, 24(9), 685–689. Markos, J., Musk, A. W., & Finucane, K. E. (1988). Functional similarities of asbestosis and cryptogenic fibrosing alveolitis. Thorax, 43(9), 708–714. Preisser, A. M., & Ochmann, U. (2011). Cardiopulmonary exercise testing in occupational medical fitness examination and assessment. Pneumologie, 65(11), 662–670. doi:10.1055/s-00311291463.
ORIGINAL PAPER
Cardiopulmonary Exercise Capacity and Ventilation Effectiveness in Patients after Clinical Cure of Acute Irritant Gas Poisoning Rong Yan • Wenlan Yang • Jinming Liu • Beilan Gao • Kongrong Guo • Daoyuan Sun
Published online: 6 December 2014 Ó Springer Science+Business Media New York 2014
Abstract The aim of this study is to assess the medium to long-term effect of acute irritant gas poisoning on cardiopulmonary exercise function in patients after clinical cure. Fourteen patients after an average of 18.5 months of clinical cure of acute irritant gas poisoning were recruited, and 14 healthy individuals were selected as control. All subjects were examined by resting pulmonary function testing (RPFT), cardiopulmonary exercise testing (CPET), and arterial blood gas (ABG) analysis. No statistically significant differences were found between poisoning and control groups for baseline parameters (age, height, and weight) or ABG values (pH, PaO2, PaCO2, and SaO2) (P [ 0.05). For most RPFT parameters, including FEV1/FVC, FEV1, FEV1%pred, RV/TLC, DLCO%, and FVC%, no statistically significant differences were observed between
poisoning and control groups (P [ 0.05). However, MVV% was significantly lower in poisoning group compared with healthy individuals (P \ 0.05). Statistically significant differences were observed for some CPET parameters, including peak VO2, peak VO2/kg, peak VE, and lowest VE/VCO2 (P \ 0.05), and peak load, VD/VT, and peak PETCO2 (P \ 0.01) between the two groups. However, there were no statistically significant differences in peak VO2%pred or peak O2 pulse between poisoning and control groups (P [ 0.05). Compared with controls, patients with acute irritant gas poisoning had decreased cardiopulmonary exercise capacity and ventilation effectiveness after clinical cure. Keywords Acute poisoning Irritant gas Cardiopulmonary exercise testing Ventilation effectiveness
Rong Yan and Wenlan Yang contributed equally to this study. R. Yan K. Guo Department of Occupational Poisoning, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China W. Yang Pulmonary Function Test Room, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China J. Liu (&) Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China e-mail: [email protected] B. Gao (&) D. Sun Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China e-mail: [email protected]
Introduction Irritant gases such as ammonia, nitrogen oxides, nitric acid, and hydrogen sulfide, when exposed to human body, can cause eye irritation or chemical eye burns [1], allergic contact dermatitis [2], and more seriously, the airway injury [3]. Acute exposure to high concentrations of toxic gas over a short time is characteristic of industrial accident, which poses as a global issue in certain professional lines [4]. Mild cases of irritant gas injury are manifested as respiratory inflammation, whereas severe cases are associated with toxic pulmonary edema or even acute respiratory distress syndrome (ARDS), potentially causing death. According to a report on acute occupational poisoning in China, irritant gas poisoning accounts for a large proportion of occupational poisoning [4, 5]. During 1989–2003,
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92 irritant gas poisoning accidents with a total of 1,330 cases and 72 deaths were reported in 23 provinces, autonomous regions, and municipalities in China; the annual average number of irritant gas poisoning accidents was 6.1, accounting for 18 % of the nation’s average number of poisoning accidents in the same period; the annual average number of irritant gas poisoning cases of 88.7 with 4.8 deaths, accounting for 5.4 % of total poisoning mortality rates [5]. Fortunately, if treated timely and correctly, poisoning symptoms in patients with toxic pulmonary edema can be controlled in 2–3 days, the associated X-ray changes disappear in approximately 1 week, and most the patients can recovery fully, although interstitial fibrosis may persist in specific cases. Despite of the high significance, few follow-up studies have been reported on the cardiopulmonary function in patients after clinical cure of acute irritant gas poisoning. Therefore, we aimed in this study to investigate cardiopulmonary exercise function in patients after clinical treatment of acute irritant gas poisoning, to assess the medium to long-term effect of acute irritant gas poison on human health. We used the cardiopulmonary exercise testing (CPET) as the main detecting measure for objective evaluation of cardiopulmonary functional reserve and exercise tolerance. Moreover, routine pulmonary function testing (RPFT) and arterial blood gas (ABG) analysis were also applied, and the results were compared with those collected from healthy individuals, in order to examine the impact of irritant gas poisoning on exercise tolerance and ventilation effectiveness.
Methods Patient Selection In this prospective cohort study, 14 patients with acute irritant gas poisoning (poisoning group) were selected from the intoxication department of our hospital from February 2009 to December 2012. The patients were males, 33–64 years old (average, 50.21 ± 7.96), 164.86 ± 4.06 cm in height, and 67.07 ± 5.23 kg in weight. Diagnosis and grading of patients were based on GBZ 73-2009 Diagnostic Criteria of occupational acute toxic respiratory system disease [6]. The patients included 10 cases of severe poisoning and 4 cases of moderate poisoning, respectively. All 14 cases had acute toxic pulmonary edema caused by exposure to irritant gases, including toxic nitrogen oxides, nitric acid, and hydrogen sulfide. The patients were admitted into the hospital several hours to 2 days after exposure to the above-mentioned irritants. Clinical cure was achieved by hormone administration, oxygen therapy,
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infection prevention, antioxidant treatment, stomach protection, and supporting therapy. The patients were clinically examined at follow-up appointments during 4–24 months, in average 18.5 months. Chest computed tomography (CT) scan showed that the original oozing lesions in both lungs were absorbed in cured patients; small cord-like shadows persisted in 2 patients only; and diffuse, tiny miliary nodules were found in one patient despite the obvious absorption of primary lesion. The exclusion criteria comprised respiratory diseases before the poisoning accident and pre-existing severe diseases of muscle and cardiovascular, nervous, and endocrine systems. The control group included 14 healthy male volunteers, matched for gender, age, height, and body weight with patients group. Inclusion criteria were no obvious heart, lung, bone, joint, muscle, nerve, or endocrine system disease. The study protocols were reviewed and approved by the ethics committee of our hospital and all subjects provided signed informed consent. RPFT Procedure RPFT was conducted at follow-up appointments using a Master Screen Diffusion modular spirometer (Jaeger, Germany). After rigorous calibration of the equipment, acceptable RPFT was completed in each subject at least three times at 1 min interval. The detection error was \5 % and the best values of detection parameters were recorded. RPFT parameters included forced expiratory volume in one second/forced vital capacity (FEV1/FVC), forced expiratory volume in one second (FEV1), percentage of forced expiratory volume in the first second in the predicted value (FEV1%pred), ratio of residual volume to total lung capacity (RV/TLC), diffusion capacity for carbon monoxide of lung (DLCO%), percentage of forced vital capacity in the predicted value (FVC%pred), and maximal voluntary ventilation% (MVV%pred). The formula of RPFT predicted value used in this study referred to that of normal predicted value of lung function in Chinese adults, as established in 1988. CPET Procedure CPET was carried out using a Master Screen-CPX test system (Jaeger, German). The flow sensor and gas analyzer were calibrated before use. A ramp-incremental symptomlimited CPET test was conducted by selecting different loads (10–25 W/min) according to the disease situation of patients, pulmonary function and the related preset programs, providing 8–12 min of exercise time. During the entire CPET test, dynamic monitoring was carried out on 12-lead electrocardiogram (ECG) for blood pressure, pulse oxygen saturation, and pulmonary ventilation. Raw data of
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gas (CO2 and O2) exchange were recorded using the breathby-breath method, and the anaerobic threshold was determined using the V-slope method [7]. The mean data for every 10 s interval were used for various graphing and subsequent calculations [8–10]. The CPET test was suspended in the following cases: (1) ECG indicates ST-segment depression of 2 mm accompanied by chest pain or STsegment depression of 3 mm without chest pain, frequent premature ventricular beat, and second- and third-degree atrioventricular block; (2) systolic blood pressure C 250 mmHg and/or diastolic blood pressure C 120 mmHg, and decrease in blood pressure relative to baseline blood pressure C 30 mmHg; and (3) pulse oxygen saturation B 80 %. Most subjects were willing to end the test due to leg pain, exhaustion, or breathing difficulties. The following parameters were read and recorded: peak load, peak O2 uptake (peak VO2), percentage of peak VO2 in the predicted value (peak VO2%pred), peak VO2 per kilogram (peak VO2/kg), peak ventilatory capacity (peak VE), peak O2 pulse, lowest ventilatory equivalent of CO2 (lowest VE/VCO2), physiologic dead space/tidal volume (VD/VT), and peak end-tidal CO2 partial pressure (peak PETCO2). The formula of CPET predicted value referred to the CPET guidelines issued by the American Thoracic Society/ American College of Chest Physicians (ATS/ACCP) in 2003 [11]. ABG Analysis On the same day of RPFT and CPET, arterial blood was drawn from radial artery of the forearm for each subject. Blood samples were analyzed using an automatic blood gas analyzer (Radiometer ABL800, Denmark). Arterial blood pH, oxygen partial pressure, CO2 partial pressure, and oxygen saturation values were read and recorded. Statistical Analysis Data analysis was conducted using the Statistical Package for the Social Sciences 13.0 (SPSS, Chicago, IL, USA). All data are presented as mean ± standard deviation. The values obtained for each parameter were compared between groups by the independent sample t test. P \ 0.05 was considered statistically significant, and P \ 0.01 was considered highly statistically significant.
Results Baseline Characteristics and ABG Data of the Poisoning and Control Groups In this study, both poisoning and control groups comprised 14 males. The patients in the poisoning group and control
791 Table 1 Baseline characteristics and partial results of blood gas analysis in poisoning and control groups (mean ± standard deviation) Variable
Poisoning group
Control group
Individuals
14
14
P value
Age (year)
50.21 ± 7.96
50.50 ± 2.50
[0.05
Height (cm)
164.86 ± 4.06
165.43 ± 2.41
[0.05
Weight (kg)
67.07 ± 5.23
66.93 ± 8.50
[0.05
pH
7.45 ± 0.18
7.44 ± 0.12
[0.05
PaO2 (mmHg) PaCO2 (mmHg)
90.36 ± 6.22 37.31 ± 4.14
91.74 ± 5.24 38.39 ± 3.06
[0.05 [0.05
SaO2 (%)
97.19 ± 0.66
96.96 ± 0.63
[0.05
Blood gas analysis
individuals were 50.21 ± 7.96 and 50.50 ± 2.50 years old, respectively. In the poisoning group, patients were 164.86 ± 4.06 cm tall and weighed 67.07 ± 5.23 kg, whereas height and weights of control individuals were 165.43 ± 2.41 cm and 66.93 ± 8.50 kg, respectively, as shown in Table 1. These data were comparable between the two groups, with no statistically significant differences in terms of age, height, or weight (P [ 0.05). ABG parameters were not altered in the poisoning group, including PaO2 (90.36 ± 6.22 vs. 91.74 ± 5.24 mmHg for controls, P [ 0.05), PaCO2 (37.31 ± 4.14 vs. 38.39 ± 3.06 mmHg for healthy individuals, P [ 0.05), and SaO2 (97.19 ± 0.66 vs. 96.96 ± 0.63 % for controls, P [ 0.05), all within normal ranges. These data demonstrated that no obvious hypoxemia, CO2 retention, or acid–base imbalance was present in either group (Table 1). Effective Treatment of Patients with Acute Irritant Gas Poisoning In the poisoning group, clinical symptoms such as cough, chest tightness, and shortness of breath were generally eliminated in the 14 patients after active treatment. Additionally, the positive signs and dry/wet rales of lung disappeared and the results of imaging tests (chest radiograph and chest CT) were significantly improved, complying with the clinical cure criteria. PFT Data of the Poisoning and Control Groups PFT data were comparable for most parameters in poisoning and control groups with, respectively, 78.53 ± 4.89 and 79.71 ± 5.35 % (FEV1/FVC), 93.64 ± 12.23 and 98.71 ± 8.94 % (FEV1%pred), 2.76 ± 0.46 and 3.01 ± 0.38 L (FEV1), 98.93 ± 12.65 and 103.39 ± 10.86 % (FVC), 35.36 ± 5.98 and 33.30 ± 1.37 % (RV/TLC), and 106.95 ± 24.31 and 116.26 ± 16.57 % (DLCO), showing no significant differences (P [ 0.05). These data indicated
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Table 2 Pulmonary function data in poisoning and control groups (mean ± standard deviation)
CPET Data of the Poisoning and Control Groups
Variable
We found that peak VO2, peak VO2/kg, and peak VE were lower in the poisoning group with 1567.07 ± 452.40, 23.33 ± 7.29, and 52.14 ± 16.68, respectively, compared with 1881.58 ± 328.67, 28.12 ± 3.61, and 67.83 ± 12.73, respectively, observed in healthy individuals (P \ 0.05) as shown in Table 3. In the poisoning group, peak load (108.64 ± 35.91) and peak PETCO2 (34.07 ± 7.10) were highly significantly lower than in the control group (151.43 ± 23.94 and 40.88 ± 2.04 for Peak load and PETCO2, respectively) at P \ 0.01 (Table 3). In contrast, VD/VT was markedly higher in the poisoning group (31.64 ± 5.06) than in the control group (24.76 ± 3.48), showing highly statistically significant differences (P \ 0.01). Likewise, the lowest VE/VCO2 was higher in the poisoning group than in the control group with 30.61 ± 5.23 and 27.34 ± 0.73, respectively, a statistically significant differences (P \ 0.05); there were no statistically significant differences in the peak VO2%pred (72.50 ± 19.73 vs. 81.91 ± 9.98) and peak O2 pulse (12.13 ± 1.86 vs. 12.53 ± 0.92) between the two groups (P [ 0.05) as shown in Table 3.
Poisoning group
Control group
P value [0.05
FEV1/FVC (%)
78.53 ± 4.89
79.71 ± 5.35
FEV1%pred (%)
93.64 ± 12.23
98.71 ± 8.94
[0.05
2.76 ± 0.46
3.01 ± 0.38
[0.05 [0.05
FEV1 (L) FVC%
98.93 ± 12.65
103.39 ± 10.86
MVV%pred
91.66 ± 20.24
106.28 ± 17.08*
\0.05
RV/TLC (%)
35.36 ± 5.98
33.30 ± 1.37
[0.05
106.95 ± 24.31
116.26 ± 16.57
[0.05
DLCO%
* Compare to the control group, p \ 0.05 FEV1/FVC forced expiratory volume in one second/forced vital capacity, FEV1%pred percentage of forced expiratory volume in the first second in the predicted value, MVV%pred maximal voluntary ventilation%, RV/TLC ratio of residual volume to total lung capacity, DLCO% diffusion capacity for carbon monoxide of lung, FVC% percentage of forced vital capacity
Table 3 Cardiopulmonary exercise data in poisoning and control groups (mean ± standard deviation) Variable
Poisoning group
Control group
P value
Peak load (W)
108.64 ± 35.91
151.43 ± 23.94** \0.01
Peak VO2 (mL/ min)
1567.07 ± 452.40
1881.58 ± 328.67* \0.05
Peak VO2%pred
72.50 ± 19.73
81.91 ± 9.98
[0.05
Discussion
Peak VO2/kg (mL/min/kg)
23.33 ± 7.29
28.12 ± 3.61*
\0.05
Peak VE (L/ min)
52.14 ± 16.68
67.83 ± 12.73*
\0.05
Peak PETCO2 (mmHg)
34.07 ± 7.10
40.88 ± 2.04**
\0.01
Peak O2 pulse (mL/beat)
12.13 ± 1.86
12.53 ± 0.92
[0.05
Lowest VE/ VCO2
30.61 ± 5.23
27.34 ± 0.73*
\0.05
VD/VT (%)
31.64 ± 5.06
24.76 ± 3.48**
\0.01
Irritant gases cause health ailments at various sites of the body, including eyes, skin, and lungs [5]. This is a global issue as evidenced by respiratory risks linked to industrial environment and work conditions in certain professions [7]. The effects of such irritants are poorly understood, especially after treatment. Therefore, this study aimed to assess the cardiopulmonary function in patients after clinical treatment of acute irritant gas poisoning. The data demonstrated that patients cured from poisoning had decreased cardiopulmonary exercise capacity and ventilation effectiveness. Among the respiratory diseases related to irritant gas inhalation, toxic pulmonary edema and ARDS are two most severe complications that lead to loss of the labor force. Although a small number of studies have investigated pulmonary function in patients with irritant gas poisoning in China, their follow-up periods are relatively short. Zhou et al. [12] studied the changes in pulmonary function in 36 patients after clinical cure of acute irritant gas poisoning and found that pulmonary function was significantly recovered post treatment. Fu et al. reported 15 cases of acute toxic pulmonary edema related to irritant gas poisoning, of which 4 cases of ARDS retained pulmonary fibrosis and mainly showed pulmonary ventilation hypofunction. In the present study, data were collected from 14 patients after clinical cure of acute pulmonary edema related to
* Compare to the control group, p \ 0.05 ** Compare to the control group, p \ 0.01 Peak VO2 peak O2 uptake, peak VO2%pred percentage of peak VO2 in the predicted value, peak VO2/kg peak VO2 per kilogram, peak VE peak ventilatory capacity, lowest VE/VCO2 lowest ventilatory equivalent of CO2, VD/VT physiologic dead space/tidal volume, peak PETCO2 peak end-tidal CO2 partial pressure
that the poisoning group showed no obvious differences in pulmonary function, residual volume, and diffusion function, compared with the control group. An exception was that MVV% which was significantly lower in the poisoning group (91.66 ± 20.24 %) than in healthy individuals (106.28 ± 17.08 %, P \ 0.05), although remaining within the normal range (above 80 %) (Table 2).
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irritant gas poisoning (poisoning group), and then compared the values with those of 14 healthy volunteers (control group). The interaction of age, gender, height, and weight was excluded by matching the controls. Our data showed no significant differences in the major ABG or RPFT parameters between the poisoning and control groups. Interestingly, the major ABG parameters, including PaO2, PaCO2, and pH, were within normal ranges in the poisoning group. As for the RPFT data, the major parameters for pulmonary ventilation function, residual volume, and diffusion function were slightly lower in the poisoning group than in the control group, but the differences were not statistically significant. However, in the CPET data, statistically significant differences were found in the parameters for cardiopulmonary exercise capacity and ventilation effectiveness between the poisoning and control groups, probably pointing at some residual damage not seen on CT scans. In addition, we found that peak load, peak VO2, and peak VO2/kg were lower in the poisoning group compared with the control group, suggesting that cured patients with acute irritant gas poisoning had decreased exercise tolerance. Peak load is an important parameter that reflects exercise tolerance. The poisoning group showed significantly lower peak load than controls, indicating that the cured patients could support significantly lower loads than healthy individuals during exercise. Similarly, peak VO2 and peak VO2%pred are indicators for cardiopulmonary O2 uptake of individuals at maximal exercise, and are considered gold standard for evaluating exercise tolerance [11]. Our data showed lower peak VO2 values for the poisoning group compared with controls. Although slightly lower in the poisoning group than in the control group, the peak VO2%pred was not statistically different between the two groups. Together, these results demonstrate that the patients with acute irritant gas poisoning had obviously decreased O2 uptake efficiency and exercise tolerance during aerobic exercise, compared with healthy individuals. Compared with healthy individuals, cured patients in the poisoning group had increased lowest VE/VCO2 and VD/VT with decreased peak PET CO2. Lowest VE/VCO2, VD/VT, and peak PET CO2 are indicators for ventilation effectiveness. After inhalation of irritant gases, the chemicals can directly injure respiratory tract mucosa, damage alveolar structure, and affect gas exchange, thereby causing ventilation/perfusion imbalance and increasing the physiological dead space and VD/VT, eventually leading to increase in VE/VCO2. VD/VT is an indicator for evaluating the degree of ventilation/perfusion imbalance. In normal circumstances, the volume of resting physiological dead space is approximately 1/3 that of tidal volume; during exercise, the physiological dead space declines to approximately 1/5 that of tidal volume [13]. In patients with ventilatory defect, uneven ventilation causes ventilation/
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perfusion imbalance, accounting for the relatively high VD/ VT, especially during exercise [14]. In the present study, VD/VT was higher in the poisoning group than in the control group, indicating that ventilation/perfusion imbalance persisted to a certain degree in patients after clinical cure of acute irritant gas poisoning, leading to ineffective ventilation. The resulting decline of ventilatory efficiency and impediment of CO2 discharge resulted in increase in PaCO2 and lowest VE/VCO2, and decrease in peak PET CO2. Regarding the cardiopulmonary exercise function, the 14 cured patients with acute poisoning had normal resting pulmonary function but decreased exercise tolerance and ventilation effectiveness compared with healthy individuals. A possible mechanism that causes the above changes is that inhaled irritant gas causes direct injuries to the airway, alveolar epithelial cells and capillary endothelial cells, alveolar wall, and alveolar septa, thereby damaging the lung tissue structure. In the repair process of lung injury, airway and alveolar epithelial cells form fibrosis in the lesion. Then, the stimulated endothelial cells release collagenase, in order to degrade and alter collagen on the basilar membrane. Finally, cell proliferation and collagen synthesis are promoted by the chemotaxis of cytokines and inflammatory mediators. Although the results of imaging tests and resting pulmonary function had no significant changes, the CPET data demonstrated certain damage to the cardiopulmonary exercise function. It is inferred that the fine structure of lung tissues alters after acute irritant gas poisoning, thereby affecting the cardiopulmonary exercise function. It is not known wether the decline observed in pulmonary function changes is reversible or not [15]. However, it was shown that asthma in cleaning workers is characterized by non-reversible lung function decrement [16]. The RPFT and ABG data showed no significant differences between the cured patients and healthy individuals. However, multiple CPET parameters were found at abnormal levels in the cured patients. At this point, even mild impairment of the ventilatory mechanism could cause breathing difficulties during exercise. The injury that RPFT failed to detect was reflected by the CPET parameters. Together these results indicate that CPET is more effective than other examination methods for detecting physiological changes in the respiratory system after irritant gas poisoning; it allows more accurate and detailed measurement of the exercise capacity, and has higher sensitivity and greater potential advantages in evaluating the exercise capacity and injuries in patients with irritant gas poisoning. In patients treated with combination of mediastinal radiotherapy (RT) and polychemotherapy (CT) regimens, lower exercise capacity seems to be due to a combination of decreased cardiac performance and an impairment of gas diffusion capacity [17]. Many studies have emphasized the
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value of combined CPET parameters for determining lung injury [18–22]; evaluation of the injury with the RPFT parameters has limitations [14]. The importance of CPET for the assessment of occupational disease-related functional loss was shown in people exposed to or formally affected by irritant toxic, allergenic or fibrosing dusts, gases, welding fumes, and mineral fibers [23]. One of the main limitations of this work is the low number of individuals per group, which does not allow high statistical power and generalization. Therefore, larger cohorts should be studied in order to verify these findings. In addition, the healthy individuals could not be tested during the study for changes in their respiratory tract. In summary, the exercise tolerance and ventilation effectiveness decreased in patients after clinical cure of acute irritant gas poisoning. Presently, only RPFT parameters are generally used for assessing the labor capacity of patients with occupational toxic respiratory diseases. It is worthy further investigating and researching the application of CPET parameters in such assessments. Conflict of interest
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The authors declare no conflicts of interest. 16.
References 17. 1. Cordes, A. K., Frentz, M., & Schrage, N. F. (2011). Eye irritation and chemical eye burns. Review of experimental and clinical studies. Ophthalmologe, 108(10), 910–915. doi:10.1007/s00347010-2249-x. 2. Nettis, E., Colanardi, M. C., Soccio, A. L., Ferrannini, A., & Tursi, A. (2002). Occupational irritant and allergic contact dermatitis among healthcare workers. Contact Dermatitis, 46(2), 101–107. 3. Sahu, S., Roy, B., & Moitra, S. (2013). Assessment of the lung function status of the goldsmiths working in an unorganized sector of India. Lung India, 30(1), 33–37. doi:10.4103/09702113.106131. 4. Lin, Q. H., Liu, Y. M., & Guo, J. Y. (2012). Epidemiological study of occupational diseases in Guangzhou City, China in 2001–2010. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 30(10), 759–762. 5. Du, X. Y., Zhang, M., Wang, H. Q., Li, T., Wang, H. F., Chen, S. Y., et al. (2006). Characterization of severe acute occupational poisoning accidents related to irritating gases in China between 1989 and 2003. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 24(12), 716–719. 6. Diagnostic Criteria of occupational acute toxic respiratory system disease: People’s Medical Publishing House, 2009. 7. Beaver, W. L., Wasserman, K., & Whipp, B. J. (1986). A new method for detecting anaerobic threshold by gas exchange. Journal of Applied Physiology (1985)., 60(6), 2020–2027. 8. Sun, X. G., Hansen, J. E., Beshai, J. F., & Wasserman, K. (2010). Oscillatory breathing and exercise gas exchange abnormalities
123
18.
19.
20.
21.
22.
23.
prognosticate early mortality and morbidity in heart failure. Journal of the American College of Cardiology, 55(17), 1814–1823. doi:10.1016/j.jacc.2009.10.075. Sun, X. G., Hansen, J. E., Oudiz, R. J., & Wasserman, K. (2001). Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation, 104(4), 429–435. Sun, X. G., Hansen, J. E., Garatachea, N., Storer, T. W., & Wasserman, K. (2002). Ventilatory efficiency during exercise in healthy subjects. American Journal of Respiratory and Critical Care Medicine, 166(11), 1443–1448. doi:10.1164/rccm.2202033. American Thoracic Society. (2003). ATS/ACCP Statement on cardiopulmonary exercise testing. American Journal of Respiratory and Critical Care Medicine, 167(2), 211–277. doi:10.1164/ rccm.167.2.211. Zhou, P., Li, W. P., & Wang, H. S. (2006). Pulmonary function changes before and after treatment in patients with acute intoxication from stimulant gases. Clinical Medical Journal of China, 13, 580. Wasserman, K., Van Kessel, A. L., & Burton, G. G. (1967). Interaction of physiological mechanisms during exercise. Journal of Applied Physiology, 22(1), 71–85. Karlman W, James E, Darry lY (2008). Principles of exercise testing and interpretation-including pathophysiology and clinical applications. Forth ed. Philadelphia: Lippincott Williams & Wilkinks. Vizcaya, D., Mirabelli, M. C., Orriols, R., Anto, J. M., Barreiro, E., Burgos, F., et al. (2013). Functional and biological characteristics of asthma in cleaning workers. Respiratory Medicine, 107(5), 673–683. doi:10.1016/j.rmed.2013.01.011. Rothman, N., Ford, D. P., Baser, M. E., Hansen, J. A., O’Toole, T., Tockman, M. S., et al. (1991). Pulmonary function and respiratory symptoms in wildland firefighters. Journal of Occupational and Environmental Medicine, 33(11), 1163–1167. Villani, F., Busia, A., Villani, M., Laffranchi, A., Viviani, S., & Bonfante, V. (2009). Cardiopulmonary response to exercise in patients with different degrees of lung toxicity after radio-chemotherapy for Hodgkin’s disease. Anticancer Research, 29(2), 777–783. Cotes, J. E., Zejda, J., & King, B. (1988). Lung function impairment as a guide to exercise limitation in work-related lung disorders. American Review of Respiratory Disease, 137(5), 1089–1093. doi:10.1164/ajrccm/137.5.1089. Agostoni, P., Smith, D. D., Schoene, R. B., Robertson, H. T., & Butler, J. (1987). Evaluation of breathlessness in asbestos workers. Results of exercise testing. American Review of Respiratory Disease, 135(4), 812–816. Agusti, A., Roca, J., Rodriguez-Roisin, R., Xaubet, A., & AgustiVidal, A. (1988). Different patterns of gas exchange response to exercise in asbestosis and idiopathic pulmonary fibrosis. European Respiratory Journal, 1(6), 510–516. Howard, J., Mohsenifar, Z., Brown, H. V., & Koerner, S. K. (1982). Role of exercise testing in assessing functional respiratory impairment due to asbestos exposure. Journal of Occupational and Environmental Medicine, 24(9), 685–689. Markos, J., Musk, A. W., & Finucane, K. E. (1988). Functional similarities of asbestosis and cryptogenic fibrosing alveolitis. Thorax, 43(9), 708–714. Preisser, A. M., & Ochmann, U. (2011). Cardiopulmonary exercise testing in occupational medical fitness examination and assessment. Pneumologie, 65(11), 662–670. doi:10.1055/s-00311291463.
