Incidence of asthma
This is the first nationwide study to characterize clinical characteristics and symptoms prior to SD in patients aged 1–35 years (n = 49) with uncontrolled asthma.
Following a systematic review of all death certificates, information from the National Patient Registry, and all available medical records from hospitals and GPs, we report that acute asthma attacks were the cause of death in 13 of 625 (2.1%) SD cases. Forty-one (84%) had symptoms prior to death, of which dyspnea was predominant, and 28 (57%) sought medical advice for these symptoms.
The incidence of fatal asthma attacks reported in the literature has varied significantly. Data based on death certificates from out-of-hospital deaths in persons younger than 40 years recorded in the Netherlands found asthma to be the cause of death in 37 out of 1908 SDs (1.9%) [18]. This result is consistent with the data of our study. However, another retrospective study [19] that investigated 151 cases of SD among Israeli military personnel at the age of 18 to 39 years found that fatal asthmatic attacks were the cause of death in 9% of all SD cases. The soldiers being exposed to occupational and environmental hazards that increased the risk of fatal asthma attacks could in part explain the high incidence of fatal asthma attacks in their study.
Clinical characteristics
We report a high mean BMI value (28.9 kg/m2). However, this is consistent with a recent study from our group on SCD due to coronary artery disease (age 1–35 years), in which we also report a high mean BMI of 26.4 kg/m2 [14].
The presence of excess abdominal fat decreases lung volume and affects the function of the diaphragm (increasing the likelihood of it suffering fatigue during stressful activity), and it has also been demonstrated that obesity increases the risk of suffering from uncontrolled asthma [20]. It is therefore likely that the high mean BMI in our study increased the severity of the patients’ asthma and may have influenced their death.
SCD and asthma
SCD in persons aged 1–35 corresponds to approximately 75% of all SDs in this age group [8].
Our results indicate that 63% of the SDs of patients with uncontrolled asthma are due to SCD, which is actually lower than in the general population. This may be attributed to the fact that a high proportion of fatal asthma attacks was reported as the cause of death in our study.
Medical history
We report that a seemingly large proportion of the patients (n = 24, 49%) had a previously known disease besides asthma. It has been reported that SD at an age of 1–20 years was attributed to a previously diagnosed condition in 53% of the SD cases [21]. When asthma diagnoses were excluded from this previous study, 41% had a previously known disease, which is similar to the results of our study.
Poor adherence to medication in patients with asthma has been shown to be significantly increased when psychological morbidity is present [22]. According to our study, 20% of the patients had been diagnosed with a psychiatric disease, which appears to be rather high. However, recent data based on interviews with 21,425 persons > 18 years old from six different European countries showed (consistent with our findings) that one in four of the respondents reported a lifetime occurrence of any mental disorder [23]. Furthermore, we have also reported that psychiatric disorders were prevalent in 18% of a randomly selected group of young persons who died in accidents [14].
Symptoms prior to death
We report a high prevalence of symptoms prior to death (n = 41, 84%), of which dyspnea was predominant. In contrast to our findings, it has previously been reported that 35% of SDs among military personnel aged 18 to 39 years in the Israeli army had symptoms at some point prior to death [19]. These symptoms included syncope, chest pain, palpitations, recent febrile disease, dyspnea, gastrointestinal symptoms, headache, and visual disturbances (in the prior two weeks). Another study [24] reported prodromal symptoms in 54% of persons < 40 years old suffering from SD. Prodromal symptoms in this study had no time limit before death, in contrast to our study, and symptoms were defined as any change from normal health status that was considered noteworthy by the subject and reported to family, friends or medical authorities. However, it is notable that subjects with previously diagnosed underlying diseases (such as asthma) were excluded from the study.
The high prevalence of symptoms prior to death in our study compared with the abovementioned studies can be attributed to the high occurrence of dyspnea in our study, which is naturally expected to be present in a population consisting of young persons with uncontrolled asthma.
If we exclude the persons that exclusively suffered from dyspnea in our study, 18 (37%) had symptoms prior to death, which is more consistent with the abovementioned studies.
Although we extracted information from all possible sources, the amount of prodromal symptoms might have been underestimated due to only 53% of the SDs being unwitnessed.
Contact with the healthcare system
We found that 41 of patients (84%) had symptoms prior to death and that just half of the patients sought medical attention, of which 17 (35%) sought medical advice from their GP and 16 (33%) from the ED. In a study by Tough et al. [25], it was previously reported that 87% of patients had contact with the hospital prior to death, which appears rather high compared with our study. There is, however, a discrepancy in the design of the study by Tough et al. compared with ours. Tough et al. analyzed death in patients who had died solely of asthma (not necessarily defined as SD), whereas our study focuses on individuals who have been categorized as suffering from uncontrolled asthma prior to death. Furthermore, the hospital records in our study focused on the 12 months prior to death, whereas the study by Tough et al. included all previous hospital contact.
Asthma medication
It is surprising that seven patients (14%) were not taking any asthma medicine at the time of death. This may be attributed to low compliance. A recent meta-analysis concluded that monotherapy of long-acting beta-adrenoceptor agonists is associated with an increased risk of asthma mortality compared with the combination of long-acting beta-adrenoceptor agonists and inhaled corticosteroids [26]. However, none of the patients in our study used long-acting beta-adrenoceptor agonists as a monotherapy.
Study strengths and limitations
It is a limitation of our study that data were collected retrospectively. The results of our study can only be applied to persons having suffered from uncontrolled asthma prior to the event and therefore not asthma in general. Furthermore, on the basis of the available medical records, we were not able to better classify the symptomology with regards to dyspnea, chest pain, general malaise and fatigue. If more precise medical records were available, it would have been interesting to subdivide the different symptoms into, for example, mild, moderate, and severe, to better assess the symptoms.
The current study design does not allow for the identification of independent risk factors associated with uncontrolled asthma.
Asthma is very difficult to diagnose, particularly in the first early years of life because asthma masquerades are common.
A sub-analysis of the infants (≤5 years) is available as supplementary data. However, because of the low number of patients (n = 5) in this age group, a comparison between them and patients > 5 years would be uninformative.
Instead of solely relying on data from autopsy reports and death certificates, we furthermore retrieved and reviewed all available patient records from the GPs, and using the civil registration number, we retrieved information on prior medical history from the National Patient Registry. Information from the GP was obtained for 33 patients (67%), and together with the information from the National Patient Registry and the Danish death certificates, we therefore have very reliable combined resources to describe the 49 SD cases diagnosed with uncontrolled asthma.