No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Medical Consequences After a Fume Event in Commercial Airline Crews
Abstract
INTRODUCTION: Many questions are still being asked about the actual health effects of exposure to a fume event for airline crewmembers. To shed new light on this controversy about so-called aerotoxic syndrome, we undertook a large-scale epidemiological study.
METHODS: We present a retrospective cohort study involving 14,953 crewmembers, including 2577 exposed to a fume event and 12,376 matched controls to estimate the hazard ratio of a subsequent sickness.
RESULTS: Prevalence of diseases that could be related to the fume event based on “possible” or “probable” level and date of occurrence after the fume event was for exposed (controls): neurological 2.9% (2.9%), psychiatric 2.5% (2.4%), vegetative 1.8% (1.5%), irritative 5.1% (4.5%), and functional 2.8% (3.2%). Differences were not significant. Incidences of having any related disease are estimated at 1552 per 100,000 person-years for exposed and 1497 per 100,000 person-years for controls, with a nonsignificant hazard ratio of 1.04 (0.86–1.25) in the Cox model. A subset of 2577 matched pairs exposed/control allowing specific statistical tests for paired data confirmed the lack of difference between exposed and controls: matched-pair risk ratio for any fume event related disease was 1.07 (0.85–1.34).
DISCUSSION: Our results clearly show that fume events are not associated with significant clinical consequences for cabin and cockpit crew. This work does not support the proposal of an “aerotoxic syndrome” in association with exposure to fume events.
Klerlein M, Dubiez L. Medical consequences after a fume event in commercial airline crews . Aerosp Med Hum Perform. 2025; 96(1):12–17.
Thermally degraded engine oil and hydraulic fluid fumes contaminating aircraft cabin air conditioning systems have been well documented since the 1950s. Whilst organophosphates have been the main subject of interest, oil and hydraulic fumes in the air supply also contain ultrafine particles, numerous volatile organic hydrocarbons and thermally degraded products. We review the literature on the effects of fume events on aircrew health. Inhalation of these potentially toxic fumes is increasingly recognised to cause acute and long-term neurological, respiratory, cardiological and other symptoms. Cumulative exposure to regular small doses of toxic fumes is potentially damaging to health and may be exacerbated by a single higher-level exposure. Assessment is complex because of the limitations of considering the toxicity of individual substances in complex heated mixtures.
There is a need for a systematic and consistent approach to diagnosis and treatment of persons who have been exposed to toxic fumes in aircraft cabins. The medical protocol presented in this paper has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of persons suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.
Introduction: “Aerotoxic syndrome” is a debated entity. Regulatory authorities consider long-term health effects to be an unlikely consequence of exposure to contaminated air because several air quality monitoring studies report low concentrations of toxic chemicals in cabin air. We describe two pilots and one flight attendant, who developed ill health during their flying career which improved after cessation of flying.
Case details: The most frequently reported symptoms were headache, balance problems, fatigue, gastro-intestinal complaints and cognitive impairment. One of these patients had reduced levels of butyrylcholinesterase after a flight suggesting exposure to organophosphate compounds had occurred. All three were found to have elevated neuronal and glial auto-antibodies, biomarkers of central nervous system injury, and all three had genetic polymorphisms of paraoxonase (PON-1) and two of cytochrome P450, leading to a reduced ability to metabolize organophosphate compound (OPs).
Discussion: A similar constellation of symptoms has been described in other studies of aircrew, although objective evidence of exposure is lacking in most of these studies. Reduced levels of butyrylcholinesterases in one of our cases is suggestive of causation and elevated neuronal and glial autoantibodies provide objective evidence of damage to the central nervous system. We consider further research is warranted.
Background: Concerns related to adverse
health effects experienced by aircrew exposed
to aircraft contaminated air have been ongoing
for over 6 decades. Unfiltered breathing
air is supplied to the cabin via the engine
compressor. The likelihood that oil leaking
over the engine oil seals may enter the cabin
air supply has prompted continuing debate
about the hazards associated with exposure
to neurotoxic substances and to the thermally
degraded or pyrolysed mixture. In this study,
we undertook an in-depth investigation
of aircrew involved in suspected aircraft
contaminated air events.
Methods: Two studies were conducted to
review the circumstances and symptoms of
a cohort of aircrew working in the pressurized
air environment of aircraft. A table of effects
was then used for categorizing symptoms and
reviewing other sources of data related to
aircraft fluids and selected other conditions.
Results: Both acute and chronic exposures
to neurotoxic and a wide range of thermally
degraded substances were confirmed, along
with a clear pattern of acute and chronic
adverse effects. The latter were supported
by medical findings and diagnoses, notably
involving the neurological, neurobehavioural
and respiratory systems.
Conclusion: A clear cause and effect
relationship has been identified linking the
symptoms, diagnoses and findings to the
occupational environment. Recognition of this
new occupational disorder and a clear medical
investigation protocol are urgently needed
Toxicology is a new science, the complexities of which have been highlighted in the papers contained within this special section. Our understanding of the mechanisms through which various chemicals interfere with nervous system function is constantly evolving and research is unable to keep up with the speed with which new chemicals are produced and put onto the market. Thus there are often controversies surrounding the health-effects of commercially available compounds and disagreement around what constitutes safe exposure limits. This article will introduce readers to an emerging concern in this field, the potential risk to health of toxic fumes in airplane cabins. We explore the challenges and methodological issues encountered by researchers who have tried to investigate this issue and highlight the need for further research on this topic. We hope this article will promote discussion amongst academics and clinicians, and lead to the identification of creative solutions to the methodological issues encountered to date.
Materials used in the operation of aircraft may contain hazardous ingredients, some with significant toxicities, and need care in handling and use. Some maintenance or operational activities, such as leaks or poorly controlled maintenance procedures, can, through contamination of aircraft cabin air, produce unwanted exposures to personnel and passengers. Occasionally, such exposures (either short term intense or long term low level) may be of a magnitude to induce symptoms of toxicity. The symptoms reported by exposed individuals are sufficiently consistent to indicate the possibility of a discrete occupational health condition, termed aerotoxic syndrome. Features of this syndrome are that it is associated with air crew exposure at altitude to atmospheric contaminants from engine oil or other aircraft fluids, chronologically juxtaposed by the development of a consistent symptomology of irritancy, sensitivity and neurotoxicity. This syndrome may be reversible following brief exposures, but features are emerging of a chronic syndrome following moderate to substantial exposures.
- Although the air from the turbine engines of commercial jet aircraft is used chiefly for propulsion some is also used to refresh and replenish air in the cabin.- As a result of oil-seal leakage, pyrolysed engine oil or lubricating oil can contaminate cabin air via the aircraft's ventilation system, and flight crew and passengers can then inhale the combusted fumes.- Exposure to emissions from cabin air, whether polluted or not, is associated with certain health risks.- This phenomenon is known as the aerotoxic syndrome or ´cabin contamination´.- The symptoms are non-specific, consisting predominantly of fatigue and mild cognitive impairment.- Possible adverse health effects are attributed factors including organophosphate tricresyl phosphate, a component of aircraft engine oil that is potently neurotoxic.
Methods for measurements and the potential for occupational exposure to organophosphates (OPs) originating from turbine and hydraulic oils among flying personnel in the aviation industry are described. Different sampling methods were applied, including active within-day methods for OPs and VOCs, newly developed passive long-term sample methods (deposition of OPs to wipe surface areas and to activated charcoal cloths), and measurements of OPs in high-efficiency particulate air (HEPA) recirculation filters (n = 6). In total, 95 and 72 within-day OP and VOC samples, respectively, have been collected during 47 flights in six different models of turbine jet engine, propeller and helicopter aircrafts (n = 40). In general, the OP air levels from the within-day samples were low. The most relevant OP in this regard originating from turbine and engine oils, tricresyl phosphate (TCP), was detected in only 4% of the samples (min-max <LOQ-0.29 µg m(-3)). TCP was however detected in 39% of the wipe samples (n = 56) and in all HEPA-filters. Other OPs, as dibutylphenyl phosphate (DBPP) and tri-n-butyl phosphate (TnBP) originating from hydraulic oils were more prominent in the samples, illustrated by determination of TnBP in all of the within-day samples collected from airplanes (n = 76, min-max 0.02-4.1 µg m(-3)). All samples were collected under normal flight conditions. However, the TCP concentration during ground testing in an airplane that had experienced leakage of turbine oil with subsequent contamination of the cabin and cockpit air, was an order of magnitude higher as compared to after engine replacement (p = 0.02).
In most airplanes, cabin air is extracted from the turbine compressors, so-called bleed air. Bleed air can become contaminated by leakage of engine oil or hydraulic fluid and possible neurotoxic constituents, like triphenyl phosphate (TPhP) and tributyl phosphate (TBP). The aim of this study was to characterize the neurotoxic hazard of TBP and TPhP, and to compare this with the possible hazard of fumes originating from engine oils and hydraulic fluids in vitro. Effects on spontaneous neuronal activity were recorded in rat primary cortical cultures grown on microelectrode arrays following exposure for 0.5h (acute), and 24h and 48h (prolonged) to TBP and TPhP (0.01 - 100µM) or fume extracts (1 - 100µg/mL) prepared from four selected engine oils and two hydraulic fluids by a laboratory bleed air simulator. TPhP and TBP concentration-dependently reduced neuronal activity with equal potency, particularly during acute exposure (TPhP IC50: 10 - 12µM; TBP IC50: 15 - 18µM). Engine oil-derived fume extracts persistently reduced neuronal activity. Hydraulic fluid-derived fume extracts showed a stronger inhibition during 0.5h exposure, but the degree of inhibition attenuates during 48h. Overall, fume extracts from hydraulic fluids were more potent than those from engine oils, in particular during 0.5h exposure, although the higher toxicity is unlikely to be due only to higher levels of TBP and TPhP in hydraulic fluids. Our combined data show that bleed air contaminants originating from selected engine oils or hydraulic fluids exhibit neurotoxic hazard in vitro, with fumes derived from the selected hydraulic fluids being most potent.
INTRODUCTION: Pilots' mental health has received increased attention following Germanwings Flight 9525 in 2015, where the copilot intentionally crashed the aircraft into the French Alps, killing all on board. An investigation of this incident found that the pilot had a depressive disorder.METHODS: This systematic review investigated peer reviewed studies of pilot mental health published since 1980. A total of 58 papers were identified.RESULTS: Two main methodologies have been employed: questionnaires and database record searches. Anxiety, depression, and suicide were the most commonly investigated mental health conditions. There were almost an equal number of studies that found a higher prevalence of psychological symptoms in pilots as those that found a lower prevalence, relative to controls or the general population. Prevalence rates were higher in studies relying solely on questionnaires than in studies employing database record searches.DISCUSSION: Prevalence estimates are closely associated with methodology, so it is difficult to determine the true rate. Factors that might account for low prevalence estimates include under-reporting of symptoms by pilots and a reluctance to diagnose on the part of health professionals. Factors that might account for high prevalence estimates include anonymous assessment, the use of questionnaires that do not align with clinical disorders, and inconsistent cut-off scores. It is recommended that future studies on prevalence use well-validated clinical measures, and that more research be conducted on the effects of particular disorders on job performance.Ackland CA, Molesworth BRC, Grisham JR, Lovibond PF. Pilot mental health, methodologies, and findings: a systematic review. Aerosp Med Hum Perform. 2022; 93(9): 696-708.
Occupational exposure to oil fumes, organophosphates, halogenated flame retardants, and other volatile and semi-volatile contaminants is a concern within the aviation industry. There is no current consensus on the risk attributed to exposure to these chemical classes within the aircraft cabin. Contaminant concentrations rarely exceed conventional air quality guidelines, but concerns have been raised about these guidelines' applicability within the aircraft environment. This systematic review, the largest and most comprehensive completed to date on the subject matter, aims to synthesize the existing research related to chemical and other exposures inside the aircraft cabin to determine the occupational risk that may be attributed said exposure, as well as, determine knowledge gaps in source, pathway, and receptor that may exist. The Science Direct, Scopus, and Web of Science databases were queried with five search terms generating 138 manuscripts that met acceptance criteria and screening.. Several potential areas requiring future examination were identified: Potable water on aircraft should be examined as a potential source of pollutant exposure, as should air conditioning expansion turbines. Historical exposure should also be more fully explored, and non-targeted analysis could provide valuable information to comprehend the aircraft cabin exposome. Occupational risk under typical flight scenarios appears to be limited for most healthy individuals. Contaminants of concern were demonstrated to be extant within the cabin, however the concentrations under normal circumstances do not appear to be individually responsible for the symptomologies that are present in impacted individuals. Questions remain regarding those that are more vulnerable or susceptible to exposure. Additionally, establishing the effects of chronic low dose exposure and exposure to contaminant mixtures has not been satisfied. The risk of acute exposure in mitigable fume events is substantial, and technological solutions or the replacement of compounds of concern for safer alternatives should be a priority.
Quantitative assessment of human exposure to semi-volatile organic compounds (SVOC), such as tricresyl phosphates (TCP) that may originate from engine oil contamination of the cabin air, during air travel is challenging due to the technical complexity of the air supply in commercial jet aircraft. Normal flight operations involve reduced air exchange before and during takeoff, which results in increased concentrations of potential cabin air pollutants. During cruise, normal ventilation rates (> 20 h- 1) are reestablished and thus lower pollutant concentrations are also reestablished. This relationship between changes in ventilation rate and associated changes in pollutant concentrations during the departure phase is first de-scribed in the present study, although this effect was found by previous studies that investi-gated distinct flight phases.
The perception of so-called "smell events" in cabin air does not necessarily indicate the pres-ence of harmful contaminants and TCP-containing oil mist must be clearly distinguished thereof. Thus, aldehydes, VOCs, and organophosphates such as TCP were investigated. In this paper, the occurrence of TCP contamination in a bleed air free Boeing 787 (B787) aircraft is reported for the first time. The results presented here show that there are TCP sources other than bleed air from leaky engines. Furthermore, exceptional release behavior of TCP suggests that a more detailed classification for engine oil-triggered cabin air contamination (CAC) events is necessary. This study evaluated measurement data from 177 flights that were either commissioned by the EASA or conducted as part of studies with the support of Lufthansa, Condor, and British Airways.
In modern aviation, so-called fume events such as exposure to an unknown mixture of chemicals introduced into the aircraft cabin with bleed air drawn off at the engines may occur. Human exposure may result in (neuro)toxic symptoms described as so-called “aerotoxic syndrome.” Currently, among other agents organophosphates (OP) are regarded as a likely cause of the observed adverse effects. After fume events 11 flight crew members (9 female/2 male; ages 23–58 yr) were admitted for a medical examination within 5 d post exposure. Individual acetylcholinesterase (AChE) and neuropathy target esterase (NTE) activities were determined. Anamnesis and clinical findings confirmed prominent symptoms of an intoxication, including headache, cognitive difficulties, and neurological disorders, among others. Patient AChE activities ranged from 37 to 50 U/g hemoglobin (reference values: 26.7–50.9 U/g hemoglobin). Ten individuals showed NTE activities ranging from 3.14 to 6.3 nmol phenyl valerate/(min × mg protein) (reference values: 3.01–24), with one patient exhibiting low NTE activity of 1.4. Biochemical effect monitoring was applied to encompass a broad range of AChE-inhibiting compounds such as OP, carbamates, and isocyanates, or to detect inhibition of NTE. The measured AChE activities indicated a subordinate contribution of OP or related compounds to the observed symptoms. All noted NTE activities were clustered at low levels. Our data suggest a likely inhibition of NTE activities in patients after fume events, which warrants further investigation. The observed symptoms may be linked to known chemical compounds in fume events, and it is not possible to infer a direct correlation between manifestations and AChE -inhibiting compounds at this time.
Poor air quality and health complaints from flight crews operating BAe-146 aircraft, requiring admission to emergency departments on several occasions, led to an investigation into the source of these problems. Health complaints could be classified as those consistent with exposure to carbon monoxide, respiratory irritants, and possible neurological agents. Cabin air is bled off from the engine's combustion air, passes through a catalytic converter to clean the air from oil contaminants, is cooled from 550° to 50°C, and enters the cabin after it passes through an airpack unit which conditions the air as appropriate. Excessive oil leakage from oil seals overloaded the catalytic converter, allowing smoke and lubricating oil components to enter the cabin. A complaint aircraft air, during a test flight, was found to contain oil contaminants including siloxane lubricating oils, as well as methylated propane and butane ester derivatives. Tricresyl phosphates, known to be neurotoxic, were identified in bulk oil samples, but could not be demonstrated in the cabin air. Air quality measurements in a problem aircraft tested on the tarmac indicated carbon monoxide at 3 ppm and carbon dioxide at 900 ppm. Air quality measurements during normal commercial flights of three noncomplaint aircraft (two BAe-146s and one de Haviland Dash 8-100) showed no detectable levels of carbon monoxide, 800 to 2700 ppm for carbon dioxide, and 19.6 to 21.9 percent for oxygen. Carbon dioxide and oxygen levels would change predictably during takeoff and landing for the former and pressurization and depressurization for the latter. Carboxyhemoglobin levels in four individuals admitted to emergency departments ranged from 0.7 to 2.0 percent. Since no direct carbon monoxide measurements were available during these incidents, it was recommended that potential problem aircraft be equipped with datalogging carbon monoxide monitors to identify or eliminate carbon monoxide exposure as a problem.
This descriptive study reports the results of assays performed to detect circulating autoantibodies in a panel of 7 proteins associated with the nervous system (NS) in sera of 12 healthy controls and a group of 34 flight crew members including both pilots and attendants who experienced adverse effects after exposure to air emissions sourced to the ventilation system in their aircrafts and subsequently sought medical attention. The proteins selected represent various types of proteins present in nerve cells that are affected by neuronal degeneration. In the sera samples from flight crew members and healthy controls, immunoglobin (IgG) was measured using Western blotting against neurofilament triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation in levels of circulating IgG-class autoantibodies in flight crew members was found. A symptom-free pilot was sampled before symptoms and then again afterward. This pilot developed clinical problems after flying for 45 h in 10 d. Significant increases in autoantibodies were noted to most of the tested proteins in the serum of this pilot after exposure to air emissions. The levels of autoantibodies rose with worsening of his condition compared to the serum sample collected prior to exposure. After cessation of flying for a year, this pilot's clinical condition improved, and eventually he recovered and his serum autoantibodies against nervous system proteins decreased. The case study with this pilot demonstrates a temporal relationship between exposure to air emissions, clinical condition, and level of serum autoantibodies to nervous system-specific proteins. Overall, these results suggest the possible development of neuronal injury and gliosis in flight crew members anecdotally exposed to cabin air emissions containing organophosphates. Thus, increased circulating serum autoantibodies resulting from neuronal damage may be used as biomarkers for chemical-induced CNS injury. The authors thank all of the participants who volunteered to take part in this case study. The technical work of Dr. Hagir B. Suliman and the art work of Sheref M. Abou-Donia are appreciated. This study was supported in part by the Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Matching is occasionally used in cohort studies; examples include studies of twins and some studies of traffic crashes. Analysis of matched cohort data is not discussed in many textbooks or articles and is not mentioned in the Stata manuals. Risk ratios can be estimated using matched-pair cohort data with Stata's mcc command. We describe a new command, csmatch, which can produce these risk ratios and is often more convenient. We briefly review flexible regression methods that can estimate risk ratios in matched cohort data: conditional Poisson regression and some versions of Cox regression. Copyright 2004 by StataCorp LP.
Epidemiologic studies commonly use personal interviews or self-administered questionnaires as the sole source of exposure information. Comparatively little attention has been paid to the reliability and validity of exposure data obtained by these methods particularly as they relate to accuracy of recall. Accuracy of recall can be evaluated by comparing questionnaire-derived data with that obtained from another presumably more accurate source considered to be the standard. Despite the need for evaluation of the validity of exposure information obtained from questionnaires fewer than 30 studies were identified in a literature review. Furthermore the range of both medically related exposures and population subgroups evaluated is limited. Although 46% of the articles (n = 13) examined medication use the primary focus of these 13 articles was on medications associated with female reproduction: oral contraceptives estrogens and medications used during pregnancy and delivery. 21% (n = 6) of the articles examined accuracy of womens recall of reproductive events. Recall of medication use by women for indications unrelated to reproduction as well as medication use by men has received little attention. Recall of past history of chronic illness and hospitalization has been more extensively studied. In addition to the limited types of medically related exposures studied recurring methodological problems often make interpretation of the findings difficult. Problems include lack of consistent terminology the lack of consistency in analytic methods to measure agreement comparisons of interview data with medical record information sources only if a subject is classified as exposed by the medical record and whether agreement between 2 data sources should be calculated for individuals or for episodes. In summary although a fairly limited number of medically-related exposures including hormonal medications hospitalization and pregnancy-related events appear to be accurately recalled as demonstrated in the comparisons of self-reports with medical records recall of other medically-related exposures including diagnostic radiographs and history of specific chronic illnesses is not as good. Further investigations should incorporate standardized methodologies to enable comparison of results across studies.
The small air space available per person in a fully occupied aircraft passenger cabin accentuates the human bioeffluent factor in the maintenance of air quality. The accumulation of carbon dioxide and other contributions to poor air quality that can occur with inadequate ventilation, even under normal circumstances, is related to the volume of available air space per person and various ventilation rates. This information is compared with established air quality guidelines to make specific recommendations with reference to aircraft passenger cabins under both normal and abnormal operating conditions. The effects of respiration on the air quality of any enclosed space from the respiration of a resting adult are estimated using standard equations. Results are given for different volumes of space per person, for zero air exchange, and for various air change rates. The required ventilation rates estimated in this way compared closely with results calculated using a standard empirical formula. The results confirm that the outside air ventilation required to achieve a target carbon dioxide concentration in the air of an occupied enclosed space remains the same regardless of the volume of that space. The outside air ventilation capability of older and more recent aircraft is then reviewed and compared with the actual measurements of cabin air quality for these periods. The correlation between calculated and measured aircraft cabin carbon dioxide concentrations from other studies was very good. Respiratory benefits and costs of returning to the 30% higher outside air ventilation rates and 8% higher cabin pressures of the 1960s and 1970s are outlined. Consideration is given to the occasional occurrence of certain types of aircraft malfunction that can introduce more serious contaminants to the aircraft cabin. Recommendations and suggestions for aircraft builders and operators are made that will help improve aircraft cabin air quality and the partial pressure of oxygen that is available to passengers at minimal cost. Also suggested are some measures that passengers can take to help improve their comfort and decrease their risk of illness, particularly on long-haul flights.
Organophosphates in aircraft cabin and cockpit air—method development and measurements of contaminants
- K Solbu
- H L Daae
- R Olsen
- S Thorud
- D G Ellingsen
- Solbu K
Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers
- J Burdon
- L T Budnik
- X Baur
- G Hageman
- C V Howard
- Burdon J
Aerotoxic syndrome: a new occupational disease? Letter to the editor
- V Martindale
- C Cowl
- A Wagstatt
- J Singh
- A Timperley
Martindale V, Cowl C, Wagstatt A, Singh J, Timperley A. Aerotoxic syndrome: a new occupational disease? Letter to the editor. Public Health
Panorama. 2017 ; 3 ( 2 ): 198 -211. [Accessed Nov. 7, 2024]. Available from
https://who-sandbox.squiz.cloud/en/publications/public-healthpanorama/journal-issues/volume-3,-issue-2,-june-2017/original-research3.
Aerotoxic syndrome: a new occupational disease? Public Health Panorama
- S Michaelis
- J Burdon
- V Howard
Michaelis S, Burdon J, Howard V. Aerotoxic syndrome: a new occupational disease? Public Health Panorama. 2017; 3(2):198-211. [Accessed
4 Nov. 2024]. Available from https://iris.who.int/handle/10665/325308.
Aerotoxic syndrome: adverse health effects following exposure to jet oil mist during commercial flights. Towards a safe and civil society
- C Winder
- J C Balouet
Winder C, Balouet JC. Aerotoxic syndrome: adverse health effects following exposure to jet oil mist during commercial flights. Towards a safe and
civil society. Proceedings of the International Congress on Occupational
Health Conference. Brisbane: Ian Eddington; 2000 :1-36.
ICD-10: international statistical classification of diseases and related health problems : tenth revision. ICD-10
World Health Organization. ICD-10: international statistical classification of diseases and related health problems : tenth revision. ICD-10
[Internet]. 2nd ed. Geneva: World Health Organization; 2004 ; Available
from: https://iris.who.int/handle/10665/42980