Effects of intravenous infusion of theophylline drugs combined with high-flow respiratory humidifier on serum procalcitonin and lactate clearance rates in elderly patients with COPD secondary to type Ⅱ respiratory failure / 中国医师杂志

Objective:To observe the effect of theophylline intravenous drip combined with high flow respiratory humidifier on serum pro Calcitonin (PCT) and lactate clearance rate (LCR) in elderly patients with chronic obstructive pulmonary disease (COPD) secondary to type II respiratory failure.Methods:We prospectively selected 120 elderly patients with COPD secondary to type II respiratory failure who were admitted to the Affiliated Hospital of Jining Medical University from March 2020 to March 2022. They were randomly divided into the control group ( n=60) and the observation group ( n=60). The control group was treated with non-invasive positive pressure ventilation combined with theophylline intravenous drip, and the observation group was treated with high flow respiratory humidification therapy apparatus combined with theophylline intravenous drip. The sputum viscosity of the two groups was counted, and the pulmonary function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), FEV 1/FVC], blood gas analysis, respiratory mechanics, oxygen metabolism, and serum index levels, as well as the difference between acute physiology and chronic health assessment Ⅱ (APACHE Ⅱ) scores after treatment were compared between the two groups. Results:The overall sputum viscosity of the observation group was better than that of the control group ( P<0.05). Before treatment, there was no statistically significant difference in lung function and blood gas analysis indicators between the two groups (all P>0.05); After treatment, the lung function indicators, arterial partial pressure of oxygen (PaO 2), and oxygenation index (PaO 2/FiO 2) of both groups were significantly increased compared to before treatment (all P<0.05), while arterial partial pressure of carbon dioxide (PaCO 2) was significantly decreased compared to before treatment (all P<0.05), and the values of each indicator in the observation group after increasing or decreasing were significantly better than those in the control group (all P<0.05). Before treatment, there was no statistically significant difference in respiratory mechanics and oxygen metabolism indicators between the two groups (all P>0.05); After treatment, the arterial blood oxygen content (CaO 2) in the two groups was significantly higher than that before treatment (all P<0.05), while the oxygen uptake rate (ERO 2) in the two groups and the VO 2 max (VO 2Max), airway peak value, and respiratory resistance in the observation group were significantly lower than those before treatment (all P<0.05), and the values of each index in the observation group after rising or falling were significantly better than those in the control group (all P<0.05). Before treatment, there was no statistically significant difference in serum indicators and APACHE Ⅱ scores between the two groups (all P>0.05); After treatment, LCR and C-reactive protein (CRP) in the observation group were significantly higher than those before treatment ( P<0.05), while the scores of PCT, Interleukin 6 (IL-6), CRP and APACHE Ⅱ were significantly lower than those before treatment (all P<0.05), and the values of each index in the observation group after increase or decrease were significantly better than those in the control group (all P<0.05). Conclusions:Theophylline intravenous drip combined with high flow respiratory humidifier can improve respiratory mechanics, oxygen metabolism, reduce inflammatory reaction, and reduce the impact of disease on life in elderly patients with COPD secondary to type II Respiratory failure.

Advances on toxicity of polyhexamethyl guanidine / 环境与职业医学

Polyhexamethyl guanidine (PHMG) is a widely used guanidine disinfectant. Since a lung injury incident induced by humidifier disinfectant (PHMG was identified as a main component) was reported in Korea, its inhalation toxicity has attracted the attention of researchers. At present, there are few domestic studies on inhalation toxicity of PHMG. In this paper, based on the domestic and foreign studies of PHMG, the toxicities of PHMG, including inhalation toxicity and associated toxic mechanism, and other potential toxicities, such as liver toxicities, cardiovascular toxicity, immunotoxicity, and reproductive and developmental toxicity, were systematically introduced, revealing that the effects of use of PHMG in a non-standard manner on the body and its possible mechanisms, which could provide reference for the use of PHMG properly and to lay a theoretical foundation and provide a scientific basis for follow-up study.

Problems with diagnostic criteria for humidifier disinfectant lung injury (HDLI): two cases of radiologically improved HDLI

Association between use of humidifier disinfectant and allergic rhinitis in Korean children: a cross-sectional study based on the eighth Panel Study on Korean Children (PSKC)

BACKGROUND: Rhinitis was the most frequently diagnosed disorder among users of humidifier disinfectants (HDs). The aim of our study was to investigate on the relationship between allergic rhinitis (AR) and HD uses.METHODS: Our study used the data from the eighth Panel Study on Korean Children; a total of 1,540 participants were enrolled. The χ² test and multiple logistic regression analyses were conducted to debunk the association between AR and HD uses.RESULTS: In our analysis, odds ratios (ORs) of doctor-diagnosed AR increased significantly when simply the response of whether HDs were used in the past was considered. When the brands of HD were considered, ORs of doctor-diagnosed AR were found to be increased significantly for those who have used polyhexamethylene guanidine phosphate/oligo(2-[2-ethoxy]-ethoxyethyl)guanidinium-containing HDs (model 3: 1.41, 95% confidence interval [CI]: 1.02–1.95). However, once duration of usage was additionally considered, ORs of doctor-diagnosed AR increased significantly only for those who have used chloromethylisothiazolinone/methylisothiazolinone-containing HDs for more than or equal to 3 months (model 3: 2.08, 95% CI: 1.17–3.69). Further, past use of HD was associated with significantly increased ORs of AR diagnosed before 2013 (model 3: 1.35, 95% CI: 1.02–1.79).CONCLUSIONS: Results of our study suggest that past uses of HDs may be associated with an increased risk of AR.

NOTCH1 Pathway is Involved in Polyhexamethylene Guanidine-Induced Humidifier Disinfectant Lung Injuries

0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.

Psychological Responses among Humidifier Disinfectant Disaster Victims and Their Families

To substantiate psychological symptoms following humidifier disinfectant (HD) disasters, counseling records of 26 victims and 92 family members of victims (45 were bereaved) were analyzed retrospectively. Among the victims, 34.6% had Clinical Global Impression-Severity scores of over 4, which meant they were moderately ill. While anxiety/fear and depression with respiratory symptoms were frequently observed in victims and family members, chronic psychological distress such as alcohol/smoking abuse and insomnia was relatively high in bereaved family members. In conclusion, it is important to provide mental health support for victims and their families, focusing on the characteristic symptoms of each group as well as monetary compensation.

Improvement and application of the opening method of mechanical ventilator humidification tank liquid / 中国实用护理杂志

Objective@#To improve the opening method of humidifier, enhance the efficiency and success rate of opening the humidifiers.@*Methods@#Use all the recycled humidifier from respirators in the wards from 1st of May to 31st of October 2015 as control group. Use the recycled humidifiers from 1st Feb to 31st July 2016 as the test group. Use metal tools to open humidifier bottles in the control group while use the newly developed and improved opening device to open the bottles in the test group to test and compare the damage rate.@*Results@#The testing group that used the practical opening device for humidifier has a decrease in damage rate from 5.97% (16/268) to 1.22% (3/245), and this difference before and after was statistically significant (χ2=8.082, P<0.01).@*Conclusions@#The use of the opening device for humidifier can enhance the intact rate, greatly improve working efficiency and save the cost.

Analysis on application value of heated humidifier of BiPAP ventilator in the treatment of type II respiratory failure / 中国医学装备

Objective: To analyze the application value of heated humidifier and water humidifier of BiPAP ventilator in the treatment of type II respiratory failure. Methods: The clinical data of 50 patients with type II respiratory failure were statistically analyzed, and these patients were divided into heated humidifier group (adopted heated humidifier, n=25) and water humidifier group (adopted water humidifier, n=25) according to the difference of humidifying device of BiPAP ventilator. The PaO2, PaCO2, pH and the effect of humidifier for upper respiratory tract with dry sensation between pre-and post treatment were analyzed by statistical method. Results: The values of PaO2and pH of heated humidifier group were significantly higher than that of water humidifier group (t=4.303, t=3.182, P<0.05), respectively. While the PaCO2of heated humidifier group was significantly lower than that of water humidifier group (t=6.965, P<0.05). In the contrast of dry sensation of upper respiratory tract, the ratio of non-dry sensation in heated humidifier group was 84.0% (21/25) and it was 32.0% (8/25) in water humidification group, and the difference between the two groups was significant (x2=12.83, P<0.05). And the ratio of general dry sensation in heated humidifier group was 16.0% (4/25) and it was 40.0% (10/25) in water humidification group, and the ratio of heated humidifier group was significantly lower than that of water humidifier group (x2=5.02, P<0.05). Besides, the ratio of worst dry sensation in heated humidifier group was 0 and it was 28.0% (7/25) in water humidifier group, and the ratio of heated humidifier group was significantly lower than that of water humidifier group (x2=7.38, P<0.05). Conclusion: In the treatment of type II respiratory failure by using BiPAP ventilator, the application value and effect of heated humidifier is higher than that of water humidifier, so it is worthy to promote and use the heated humidifier in clinical practice.

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance.

Combined approaches using adverse outcome pathways and big data to find potential diseasesassociated with humidifier disinfectant

According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.

Humidifier disinfectant-associated specific diseases should be called together as “humidifier disinfectant syndrome”

Humidifier disinfectant (HD) damage was terrible chemical damage caused by household goods that happened in only South Korea, but still very little is known in HD damage. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchioles and alveoli because it is a specific finding, compared with other diseases. To figure out whole effects from HDs, much epidemiologic and toxicologic research is underway. HDs were shown to give rise to typical toxicologic effects on various target organs, such as skin, conjunctiva, naval mucosa, bronchial mucosa, alveoli and so on, which shared common toxicological responses. On a specific target, specific toxicologic effects existed. Diverse diseases along exposure pathways can occur at the same time with a common toxicologic mechanism and cause of HDs, which can be called as HD syndrome. To gain stronger scientific evidence about it, further epidemiological and toxicological studies should be applied.

Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant

According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.

Airway humidfi icationd urin g mechanical ventilation / 中国小儿急救医学

Humidificait on by artificial means must be provided when the upper airway is bypassed during mechanical ventilation.Enough humidification is very important during mechanical ventilation.Heated humidification( HH) and heta and moisture exchanger( HME) are the most commonly used types of artificial humidification in this situation.In this article, their advantages and disadvantages are itn roduced.HH na d HME are compared in humidification performance,effect no ventilator mechanics and association with venti-lation associated pneumonia.Depending on the clinical scenario, humidifier is reasonably selected, and the selection may changeo ver time according the treatment effect.

Inhalation Lung Injury Associated with Humidifier Disinfectants in Adults

We recently established a novel disease entity presented as progressive respiratory failure associated with the inhalation of humidifier disinfectants. In April 2011, we encountered a series of peripartum patients with complaints of respiratory distress of unknown etiology, which was an uncommon phenomenon. Accordingly, we created a multidisciplinary team comprising intensivists, radiologists, pathologists, epidemiologists, and the Korea Centers for Disease Control and Prevention (KCDC). Further, we defined the disease entity and performed a case-control study, epidemiologic investigation, and animal study to determine the etiology. The study findings indicated that the lung injury outbreak was related to the inhalation of humidifier disinfectants and showed that household chemical inhalation can cause severe respiratory failure. Following the withdrawal of humidifier disinfectants from the Korean market in 2012, no such cases were reported. This tragic event is a warning that appropriate safety regulations and monitoring for potential toxic household chemicals are critical to protect public health.

An analysis of a humidifier disinfectant case from a toxicological perspective

An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.

What must be done to prevent another humidifier disinfectant disaster?

The humidifier disinfectant disaster (HDD) was not a simple poisoning accident by biocides, but a singular disaster in history created by chemicals in household products. This disaster was a result of the failure of a system for the management of chemical and product safety. Since the management authority for chemical usage safety is different from those for chemical safety in products, many blind areas for chemical safety management in products still remain. The ‘Act on the Registration and Evaluation, etc. of Chemical Substances (ARECS)’ or the new ‘Biocidal Product Act’ must not only address the blind areas in the management system for chemical and product safety, but also prevent a second HDD. To prevent another HDD, an integrated registration, evaluation, and management system for chemicals and consumer products must be incorporated into the ‘ARECS’ as an essential part for chemical safety in consumer products.

Humidifier disinfectant lung injury, how do we approach the issues?

A large portion of the Korean population has been exposed to toxic humidifier disinfectants (HDs), and considering that the majority of the victims are infants, the magnitude of the damage is expected to be considerably larger than what has currently been revealed. The current victims are voicing problems caused by various diseases, including but not limited to lung, upper respiratory tract, cardiovascular, kidney, musculoskeletal, eye, and skin diseases, etc. However, there has been difficulty in gaining validation for these health problems and identifying causal relationships due to lack of evidence proving that toxic HD is the specific causes of extrapulmonary diseases such as allergic rhinitis. Furthermore, the victims and bereaved families of the HD case have not received any support for psychological distress such as post-traumatic stress disorder, depression, feelings of injustice, and anger caused by the trauma. In addition, because the underlying mechanisms of the toxic materials within the HDs such as polyhexamethylene guanidine phosphate, poly(oxyalkylene guanidine) hydrochloride, chloromethylisothiazolinone/methylisothiazolinone have yet to be determined, the demand for information regarding the HD issue is growing. The victims of the HD cases require support that goes beyond financial aid for medical costs and living expenses. There is a desperate need for government-led integrated support centers that provide individualized support through health screenings; in other words, we need an integrated facility that provides the appropriate social support to allow the victims to recover their physical and mental health, so as to well prepare them to return to a normal life. The implementation of such a plan requires not only the close cooperation between those departments already directly involved such as the Ministry of Environment and the Ministry of Health and Welfare, but also active support on a national scale from pan-governmental consultative bodies.

Major concerns regarding lung injury and related health conditions caused by the use of humidifier disinfectant

A total of 221 patients were evaluated to be humidifier disinfectant associated with lung injury (HDLI) through two rounds of programs through April 2015. The humidifier disinfectant (HD) brands most often associated with HDLI were found to be Oxy (n=151, 68 %) and Cefu (n=26, 17 %). Polyhexamethylene guanidine used for disinfectant for four types of HD brands including Oxy was found to be associated with the highest number of HDLI cases (n=188). Further programs are operating to identify various health effects including lung injury which may be associated with the use of HD. Not only national agencies, but also pertinent environmental health societies should cooperate in the necessary investigations so that this tragedy can be properly addressed and future incidents concerning chemicals and chemical-containing products can be prevented.

Humidifier disinfectants, unfinished stories

Once released into the air, humidifier disinfectants became tiny nano-size particles, and resulted in chemical bronchoalveolitis. Families had lost their most beloved members, and even some of them became broken. Based on an estimate of two million potential victims who had experienced adverse effects from the use of humidifier disinfectants, we can say that what we have observed was only the tip of the iceberg. Problems of entire airways, as well as other systemic effects, should be examined, as we know these nano-size particles can irritate cell membranes and migrate into systemic circulation. The story of humidifier disinfectant is not finished yet.

Development of a novel automatic water system for ventilator humidifier / 国际生物医学工程杂志

Objective To develop a novel automatic water system for ventilator humidifier.Methods By hanging the infusion apparatus high,sustained water was filled by driving force of gravity.Liquid level in the thong of the infusion apparatus was detected by the sensor,and the closing and opening of the closing clip was controlled by solenoid valve.Results The closing clip opened when the liquid level inside the ventilator humidifier fell below the lowest setting value and purified water in the infusion bottle automatically flowed to the humidifier.When the liquid level reached the highest setting level,the closing clip was automatically closed.Conclusions The developed automatic water system for ventilator humidifier is effective,convenient,inexpensive,and realized a sustained,relatively steady and a small amount of water process.Meanwhile,humidifier water is stable,heating is uniform,and gas temperature is relatively constant,which can be applied in clinical use.