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.

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

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.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Acondicionamiento del gas inhalado en pacientes con vía aérea artificial. Revisión narrativa / Humidification and heating of inhaled gas in patients with artificial airway. A narrative review

RESUMEN La instrumentación de la vía aérea del paciente crítico (tubo endotraqueal o cánula de traqueostomía) impide que ésta pueda cumplir con su función de calentar y humidificar el gas inhalado. Sumado a ello la administración de gases medicinales fríos y secos, y los altos flujos a los que se someten los pacientes en ventilación mecánica invasiva o no invasiva, generan una condición aún más desfavorable. Debido a esto es imperativo utilizar algún dispositivo para acondicionar los gases entregados incluso en tratamientos de corta duración con el fin de evitar los daños potenciales sobre la estructura y función del epitelio respiratorio. En el ámbito de terapia intensiva es habitual para esto el uso de intercambiadores de calor y humedad, como así también el uso de sistemas de humidificación activa. Para su correcta utilización es necesario poseer el conocimiento necesario sobre las especificaciones técnicas, ventajas y desventajas de cada uno de estos dispositivos ya que el acondicionamiento de los gases inspirados representa una intervención clave en pacientes con vía aérea artificial y se ha transformado en un cuidado estándar. La selección incorrecta del dispositivo o la configuración inapropiada pueden impactar negativamente en los resultados clínicos. Los integrantes del Capítulo de Kinesiología Intensivista de la Sociedad Argentina de Terapia Intensiva realizaron una revisión narrativa con el objetivo de exponer la evidencia disponible en relación al acondicionamiento del gas inhalado en pacientes con vía aérea artificial, profundizando sobre los conceptos relacionados a los principios de funcionamiento de cada uno.

ABSTRACT Instrumentation of the airways in critical patients (endotracheal tube or tracheostomy cannula) prevents them from performing their function of humidify and heating the inhaled gas. In addition, the administration of cold and dry medical gases and the high flows that patients experience during invasive and non-invasive mechanical ventilation generate an even worse condition. For this reason, a device for gas conditioning is needed, even in short-term treatments, to avoid potential damage to the structure and function of the respiratory epithelium. In the field of intensive therapy, the use of heat and moisture exchangers is common for this purpose, as is the use of active humidification systems. Acquiring knowledge about technical specifications and the advantages and disadvantages of each device is needed for proper use since the conditioning of inspired gases is a key intervention in patients with artificial airway and has become routine care. Incorrect selection or inappropriate configuration of a device can have a negative impact on clinical outcomes. The members of the Capítulo de Kinesiología Intensivista of the Sociedad Argentina de Terapia Intensiva conducted a narrative review aiming to show the available evidence regarding conditioning of inhaled gas in patients with artificial airways, going into detail on concepts related to the working principles of each one.

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.

Alterações ventilatórias durante o uso de trocadores de calor e umidade em pacientes submetidos à ventilação mecânica com pressão de suporte e ajustes nos parâmetros ventilatórios para compensar estas possíveis alterações: estudo de intervenção autocontrolado em humanos / Ventilatory changes during the use of heat and moisture exchangers in patients submitted to mechanical ventilation with support pressure and adjustments in ventilation parameters to compensate for these possible changes: a self-controlled intervention study in humans

RESUMO Objetivo: Avaliar as possíveis alterações do volume corrente, volume-minuto e frequência respiratória causadas pela utilização de trocadores de calor e umidade em pacientes submetidos à ventilação mecânica na modalidade pressão de suporte, e quantificar a variação da pressão de suporte necessária para compensar o efeito causado pelo trocador de calor e umidade. Métodos: Os pacientes sob ventilação mecânica invasiva na modalidade pressão de suporte foram avaliados utilizando umidificadores aquecidos e trocadores de calor e umidade. Caso o volume encontrado com uso de trocadores de calor e umidade fosse menor que o achado com o umidificador aquecido, iniciava-se o aumento da pressão de suporte, perante o uso de trocadores de calor e umidade, até ser encontrado um valor de pressão de suporte que possibilitasse ao paciente gerar um valor próximo do volume corrente inicial com umidificador aquecido. A análise foi realizada por meio do teste t pareado, e os valores de incremento foram expressos em porcentagem de aumento necessário. Resultados: Foram avaliados 26 pacientes. O uso de trocadores de calor e umidade aumentou a frequência respiratória, e reduziu o volume corrente e o volume-minuto, quando comparados com o uso do umidificador aquecido. Com o uso de trocadores de calor e umidade, os pacientes precisaram de um incremento de 38,13% na pressão de suporte para manter os volumes prévios. Conclusão: O trocador de calor e umidade alterou os parâmetros de volume corrente, volume-minuto e frequência respiratória, sendo necessário um aumento da pressão de suporte para compensar estas alterações.

ABSTRACT Objective: To evaluate the possible changes in tidal volume, minute volume and respiratory rate caused by the use of a heat and moisture exchanger in patients receiving pressure support mechanical ventilation and to quantify the variation in pressure support required to compensate for the effect caused by the heat and moisture exchanger. Methods: Patients under invasive mechanical ventilation in pressure support mode were evaluated using heated humidifiers and heat and moisture exchangers. If the volume found using the heat and moisture exchangers was lower than that found with the heated humidifier, an increase in pressure support was initiated during the use of the heat and moisture exchanger until a pressure support value was obtained that enabled the patient to generate a value close to the initial tidal volume obtained with the heated humidifier. The analysis was performed by means of the paired t test, and incremental values were expressed as percentages of increase required. Results: A total of 26 patients were evaluated. The use of heat and moisture exchangers increased the respiratory rate and reduced the tidal and minute volumes compared with the use of the heated humidifier. Patients required a 38.13% increase in pressure support to maintain previous volumes when using the heat and moisture exchanger. Conclusion: The heat and moisture exchanger changed the tidal and minute volumes and respiratory rate parameters. Pressure support was increased to compensate for these changes.

Humidifier Disinfectant-Associated Lung Injury: Six Years after the Tragic Event / 결핵및호흡기질환

In 2011, a cluster of peripartum patients were admitted to the intensive care unit of a tertiary hospital in Seoul with signs and symptoms of severe respiratory distress of unknown etiology. Subsequent epidemiological and animal studies suggested that humidifier disinfectant (HD) might represent the source of this pathology. Epidemiological studies, animal studies, and dose-response analysis demonstrated a strong association between HD use and lung injuries. The diagnostic criteria for HD-associated lung injury (HDALI) was defined on the basis of the clinical, pathological, and radiological attributes of the patients. The clinical spectrum of HDALI appears to range from asymptomatic to full-blown acute respiratory failure, and some patients have required actual lung transplantation for survival. The overall mortality of the exposed population was not significant, although peripartum patients and children who were admitted to the intensive care unit did show high mortality rates. Persistent clinical findings such as diffuse ill-defined centrilobular nodules and restrictive lung dysfunction were observed in some of the survivors. The findings of this review emphasize the importance of assessment of the level of toxicity of chemical inhalants utilized in a home setting, as well as the need to identify and monitor afflicted individuals after inhalational injury.

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.

Prevalence of Dry Eye Syndrome and Association with Life Behaviors in Adolescents

PURPOSE: To investigate the prevalence and risk factors of dry eye syndrome (DES) among adolescents based on the Ocular Surface Disease Index (OSDI) questionnaire. METHODS: A questionnaire survey was conducted on middle and high school students in Daejeon. DES was diagnosed by an OSDI score ≥ 13. According to the OSDI score, DES was classified as mild (13-22 points), moderate (23-32 points), or severe (33-100 points). Additionally, responses to the questions regarding adolescents' life behaviors including the duration of electronic device use per week (cellphone, computer, TV), study hours per day, sleeping hours per day, contact lenses use, glasses use, and humidifier use were analyzed to determine the associations with DES. RESULTS: Of 332 students, DES was diagnosed in 147 (44.3%), and 54 (16.3%) complained of severe DES. The prevalence of DES was higher in female students (p = 0.004), long-time electronic device users (divided on the basis of the mean value, 15.3 hours per week, p = 0.011), and contact lenses users (p = 0.001). The prevalence of DES was 53.9% in groups with ≥ 14 hours of electronic device usage time per week, 40.2% in groups with ≥ 7 hours, and 33.7% in groups with < 7 hours (p = 0.002). The duration of electronic device use per week was a significant risk factor of DES for male students, and contact lenses use was a significant risk factor of DES for female students (p = 0.009). CONCLUSIONS: The prevalence of DES was high among adolescents. Long-time electronic device usage and contact lenses wear were associated with DES and increased the risk of DES.

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 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.

Autoavaliação de aspectos respiratórios e vocais após uso do umidificador de traqueostomia em laringectomizados totais / Breathing and voice self-assessments after the use of a heat and moisture exchange in total laryngectomyzed patients

RESUMO Introdução O umidificador de traqueostomia é um dispositivo permutador de calor e umidade que pode interferir nas condições respiratórias e vocais de laringectomizados totais. Objetivo Verificar a autoavaliação de aspectos respiratórios e vocais antes e após o uso do umidificador de traqueostomia, em pacientes submetidos à laringectomia total. Métodos A amostra foi composta por 15 indivíduos acompanhados no serviço de Fonoaudiologia de um hospital oncológico, sendo uma mulher e 14 homens, com idade entre 49 e 76 anos, submetidos à laringectomia total. Foi aplicado um questionário de autoavaliação, relacionado a aspectos respiratórios e vocais antes e após o uso do umidificador de traqueostomia, durante duas semanas. Resultados Permaneceram no estudo 13 indivíduos que referiram melhora da tosse, diminuição do acúmulo de secreção e melhor qualidade respiratória e de voz esofágica, após uso do umidificador de traqueostomia. Conclusão Pacientes laringectomizados totais perceberam melhora na autoavaliação de aspectos respiratórios e vocais após duas semanas de uso do umidificador de traqueostomia.

ABSTRACT Introduction A heat and moisture exchange device could modify respiratory and vocal conditions in patients who received a total laryngectomy. Purpose To verify breathing and voice self-assessments before and after the use of a heat and moisture exchange device in patients who had received a total laryngectomy. Methods The sample included 15 subjects of the Speech Therapy department of a cancer hospital; subjects included 1 woman and 14 men aged 49 to 76 years who had undergone a total laryngectomy. Patients completed a self-assessment questionnaire about breathing and voice before and after two weeks of use of a heat and moisture exchange device. Results Thirteen individuals completed the study and reported improvement in cough, secretion accumulation, sleep, breathing, and esophageal voice after use of a heat and moisture exchange device. Conclusion Patients who had received a total laryngectomy perceived improvements in breathing and voice after two weeks of the use of a heat and moisture exchange device, as measured by self-assessment.

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.

The humidifier disinfectant case and the legislative challenges of the 20th Congress

A number of absurdities surrounding the humidifier disinfectant (HD) incident may have occurred because 1) a judicial system operates on the underlying false assumption that the involved parties are equals in knowledge, information and resource mobilization capabilities, regardless of respective real status as company or individual; 2) there is a lack of a system that mandates a company to prevent and actively manage possible catastrophes; 3) the regulatory scheme makes companies believe that as long as they are complying with the existing regulations, they have satisfied all of their responsibilities. I believe that this issue is an opportunity to bring about changes in the judicial redress system, the system of internal management of manufacturers, and the regulatory system of the government. The following regulation amendments are needed to move towards the changes stated above. First, legislation relating to victim relief that is applicable to the HD incident must be established. Second, a risk management system must be formed within the manufacturing company and to this end an institutional environment for the system must be established within regulatory framework. Furthermore, legislation must be passed that could punish companies themselves that have caused severe damage to individuals because they had failed to take necessary actions to avoid foreseeable harm. Finally, the framework of regulation must be changed so that the company, who has the necessary information regarding the product and the component chemicals used in the product, must self-directed experiment and assessment of the safety of their own products.

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.