Asthma deaths in Cardiff 1963-74: 53 deaths in hospital.

In a study of factors associated with death from bronchial asthma in hospital 53 patients were investigated. Typically the fatal attack persisted for several days before admission to hospital and normally occurred in patients with a long history of asthma. The patient or doctor often underestimated the severity of the attack. On admission most patients were severely ill, and over a third died within 24 hours. Peak flow rate and blood gases were rarely measured. Corticosteroid treatment was often underused, and patients rarely received assisted ventilation before death. Infection played a part in 14 deaths, five of them associated with assisted ventilation. Admitting asthmatics to a special respiratory ward with facilities for standardised assessment and treatment and introducing a self-admission service may help to prevent some of these deaths.     

Asthma: analysis of sudden deaths and ventilatory arrests in hospital.

The incidence of episodes of unexpected ventilatory arrest, some of which led to sudden death, was studied in 1169 consecutive hospital admissions for asthma. Of the most acute cases, 458 were initially managed in a special care unit where only one ventilatory arrest occurred. A further nine cases of arrest, three of which proved fatal, happened on general wards. Accepted clinical criteria of a severe attack were not present in those episodes occurring outside the unit, which were apparently mild attacks. The risk of sudden death could not be related to the severity of the attack but it did correlate with the presence of excessive diurnal variation in peak expiratory flow rate (PEFR). Special treatment of patients with this sign might reduce mortality.     

Death from asthma in two regions of England

The British Thoracic Association has conducted a confidential inquiry into death from asthma of adults aged 15 to 64 years resident in the West Midland and Mersey regions in 1979. Information concerning the patients, their asthma, and death was obtained by questionnaire, interview with the general medical practitioner and a relative, and from patient records. A panel of three physicians, helped by a pathologist, identified 90 patients as dying of asthma and assessed management and treatment in the last year, last month of life, and the fatal attack. They were generally chronic asthmatics, but unstable, most having suffered severe attacks previously. Corticosteroids and bronchodilator drugs were in general underprescribed or not given in sufficiently large doses. Inhaled corticosteroids and cromoglycate had frequently not been tried. The patient''s co-operation with the management of the asthma was satisfactory for only 42 of the 90 patients. For 71 of the patients the fatal attack lasted under 24 hours; of the 77 who died at home or at work, 50 did not receive any medical attention in the fatal attack. Failure to recognise the severity of the asthma by patients, relatives, and doctor often caused delay in starting appropriate treatment. The interaction of several of these adverse factors often contributed to the patient''s death. The panel considered that there were potentially preventable factors contributory to the death of 77 (86%) of the 90 patients. Within the limits of retrospective judgment the panel considered that the routine management of the asthma was often unsatisfactory as patients known to suffer severe acute attacks were often not adequately supervised or instructed in the management and treatment of their asthma. From this retrospective inquiry we concluded that closer overall supervision, including careful attention to patient education, earlier and more intensive treatment, and pre-arranged immediate admission to hospital for asthma emergencies is desirable.     

Circumstances of death from asthma.

Mortality from asthma in England and Wales has remained unchanged for at least 20 years, even in the age group 15-44. Yet in those 20 years "modern" drugs have been introduced for the treatment of asthma, such as beta 2 agonist bronchodilators and corticosteroids. Why do patients still die? Detailed review of the circumstances of 90 deaths from asthma showed that a few were inevitable but that in the remainder four main sets of circumstances in the fatal attack contributed to the death. These were, firstly, the patient''s failure to recognise the severity of the asthma; secondly, very rapid progress in the severity of the attack; thirdly, misjudgment in the management of the attack; and, fourthly, delay from many causes. Patients admitted to hospital with severe acute asthma usually survive. Those at risk of a life threatening attack should be identified and taught to monitor the severity and progress of their asthma objectively. Their direct admission to hospital should be facilitated.     

Controlled investigation of deaths from asthma in hospitals in the North East Thames region.

One hundred and thirty deaths definitely or potentially due to asthma occurring in hospitals in the North East Thames region over one year were identified from death certificates and Hospital Activity Analysis records. Thirty five of these deaths were considered after independent assessment to have been directly due to asthma. Control patients who left hospital alive after acute asthma attacks were selected and matched with cases for sex, age, and hospital. Management was compared in the two groups. Inadequate monitoring, including failure to monitor arterial blood gas values, and inadequate use of nebulised beta agonists occurred significantly more often in fatal cases. Use of sedation, inadequate treatment with steroids, exposure to potentially toxic doses of aminophylline, and inadequate clinical assessment were more common in cases than controls, but not significantly so. Failure to institute artificial ventilation contributed to seven deaths. Assessors considered important defects in management to have occurred in 83% (29/35) of the cases and 40% (14/35) of the controls. Nevertheless, most of the hospital deaths (19/35) were considered not to have been preventable. Eight other deaths in the region were attributed to the complications of asthma or its treatment. Three of these were associated with gastrointestinal bleeding and one with perforation of a duodenal ulcer. Before considering policies aimed at speeding admission to hospital of patients with acute attacks of asthma it is crucial that the general standard of hospital care offered to all patients with asthma should be improved.     

Death from asthma.

The factors associated with the deaths of 31 asthma patients were examined. The subjects, whose deaths occurred in the period 1967 through 1979, had all received some care at the Hospital for Sick Children in Toronto, but only nine died there. The greatest single cause of death was the inappropriate use of beta-agonists, with or without the concurrent use of epinephrine. In seven patients an asthma attack that occurred outside hospital progressed so rapidly that there was insufficient time for them to obtain adequate therapy. In five cases the assessment of the patient''s condition or the therapy recommended by the attending physician appeared to have been inadequate. Two patients suffered an acute attack in hopital and did not respond to treatment that appeared to have been adequate. In six cases the available information was insufficient to indicate the cause of death. Over half (18) of the deaths occurred in teenagers. Various ways of preventing death from asthma are discussed, including better education of physicians and patients, adequate management of factors that provoke bronchospasm, sufficient follow-up -- especially in teenagers -- and the use of approaches with teenagers that encourage better compliance.     

75 deaths in asthmatics prescribed home nebulisers.

The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma.     

Trends in the hospital care of acute childhood asthma 1970-8: a regional study.

In the South-west Thames Region over the period 1970-8 the number of admissions for asthma in children aged 5-14 years increased from 256 to 684, an increase of 167%. Factors associated with this trend were investigated by an analysis of routine hospital statistics and examination of case notes for 1970 and 1978 from every hospital in the region. The trend was caused partly by an increase in readmission rates. There was a more than fivefold increase in self-referrals; these patients had less severe asthma on admission and a higher readmission rate than patients referred by general practitioners. Drug management before and after admission changed considerably over the nine years, as did hospital investigations. Overall, there was little change in the level of severity on admission. The increase in admissions was not associated with a reduction in deaths from asthma in the region and occurred in spite of major advances in the drug control of asthma; this indicates an inadequacy of ambulatory care. The shift in the balance of care towards the hospital and the increasing adoption of a primary care function by the hospital indicate a need for hospitals and general practice to agree jointly on management policies for acute asthma.     

Asthma mortality in Birmingham 1975-7: 53 deaths.

Out of 83 patients studied 72 were certified as dying from asthma, and 11 aged under 45 as dying from chronic bronchitis and pneumonia. Fifty-three deaths were thought to be due to asthma. There were avoidable factors associated with several of these deaths from asthma. Recent discharge from hospital (16%), non-availability of aerosol bronchodilators (45%), underuse of corticosteroids (66%), and lack of objective measurements of airflow obstruction (100%) were found in deaths outside hospital. Inadequate initial assessment including baseline spirometry and blood gases (50%), significant underusage of corticosteroids (93%) and intravenous and nebulised bronchodilators (100%), and failure to monitor treatment objectively (100%) were found in deaths in hospital. "False-positive" and "false-negative" certifications of asthma were studied, and the findings suggest that these may lead to appreciable inaccuracy in the reporting of deaths from asthma.     

Asthma mortality: comparison between New Zealand and England.

Causes for the high mortality from asthma in New Zealand were investigated by comparing deaths from asthma in caucasian subjects aged 15-64 in New Zealand with those from asthma in the same age group in two regions in England. There were no significant differences in the accuracy of death certification. The verified asthma mortality in New Zealand (4.2/100,000) was over twice that in England. Many characteristics of patients and management, including poor compliance with treatment and deficiencies in long term and emergency care, were qualitatively similar in the two countries. New Zealand had an apparently higher rate of non-preventable deaths from asthma, suggesting a greater severity of asthma in New Zealand. In both countries, however, most deaths were associated with poor assessment, underestimation of severity and inappropriate treatment (over-reliance on bronchodilators and underuse of systemic corticosteroids), and delays in obtaining help. A greater frequency of some of these deficiencies in management remains a possible additional explanation for part of the excess mortality in New Zealand.     

Operating room deaths; an analysis of mortality in a Veterans Administration hospital over a ten-year period

A study of operating room and recovery room deaths which occurred during a ten-year period from 1948 through 1957 at one hospital revealed that there were 59 deaths associated with 57,132 surgical procedures. Factors which directly influenced the rate of operating room and recovery room death were the age of the patient and the length of operating time. Seventy-five per cent of the deaths occurred in cases in which the operation took longer than one hour. Combined anesthesia techniques may have indirectly contributed to death in some cases. Complications of operation requiring another surgical procedure sometimes occur. In this series, reoperation proved to be more hazardous in terms of mortality rate than did single operations. This is not surprising for most complications occur in the poorer risk patients. The operating room death rate steadily increased during the ten-year period studied. This increasing death rate can largely be attributed to the more intricate operations which are being done on poorer risk patients. The use of the curariform drugs had no influence on the increasing death rate.     

Illness in the family

OBJECTIVE: To update reports of increases in the rates of admission to hospital and death from asthma among children and young adults in Canada during the 1970s by examining data for the 1980s. DESIGN: Age-standardized rates were calculated from data for people less than 35 years of age at the time of death from asthma, bronchitis or other respiratory conditions (from 1980 through 1989) and at the time of admission to hospital for treatment of these diseases (from 1980 through 1988). Standardized mortality ratios were calculated with the death rate for Canada as the expected rate. SETTING: Data for all of Canada were examined by sex, age group and province. RESULTS: In contrast to sharp increases in the rate of death from asthma observed from 1970 through the early 1980s among Canadians less than 35 years of age, the rate showed no net change between 1980 and 1989; on average, there were 58 deaths in this age group annually. During the decade, the rates of death from asthma were three times higher in Saskatchewan and Alberta than in Newfoundland. The national rate of hospital admission/separation for asthma, however, increased greatly, though changes in the rate varied by province. Increases of over 90% were observed in Prince Edward Island and New Brunswick, whereas little overall change occurred in Newfoundland, Manitoba and Saskatchewan. The rate of hospital admission/separation for asthma was highest in Prince Edward Island and lowest in Manitoba and British Columbia. Although the rates of hospital admission/separation for asthma among boys aged less than 15 years of age were consistently 50% higher than those among girls of that age, the rate among people aged 15 through 34 years was twice as high among females as males. A slight decrease in the rates of death from respiratory conditions other than asthma was observed, together with a steady, fairly substantial decline in the rates of hospital admission/separation for these conditions. CONCLUSIONS: Whether there is any relation between increases in rates of admission to hospital for asthma and trends in the rates of death from asthma during the decade will require further study.     

Serum level of specific IgG antibody for aspergillus and its association with severity of asthma in asthmatic children

Aspergillosis is one of the frequent causes of exacerbation of asthma depending on the geographical regions. The specific serum IgG level for aspergillus is a major diagnostic criterion in aspergillosis.Ninety-six asthmatic patients, with mean age of 5.4 ± 3.0 years who were referred to the asthma clinic of the Mofid Children's Hospital, were enrolled in this study. Serum specific IgG for aspergillus was measured and its association with severity of asthma was evaluated.Nineteen asthmatic patients (10 females and 9 males) had aspergillus IgG antibody. Among them, severe persistent asthma and moderate persistent asthma were detected in 5 and 13 cases, respectively, whereas only one patient suffered from mildpersistent asthma. A total of 36.5% of the 96 patients had a history of atopy, while 26% had allergic rhinitis. There was an association between the severity of asthma and the presence of aspergillus IgG antibody. Moreover, the positivity for aspergillus IgG antibody was higher in older patients.Our results indicated an association between aspergillus antibody level and severity of asthma. It could be recommended that the IgG titer for aspergillus is measured in pediatric patients with asthma, whereas co-morbidity of aspergillosis and asthma increases the risk of asthma exacerbation.     

miR-1165-3p、miR-145水平在支气管哮喘患者中的表达及其临床意义

摘要 目的：探讨微小RNA（MicroRNA,miR）-1165-3p、miR-145水平在支气管哮喘患者中的表达及其临床意义。方法：收集2021年1月-2022年3月中国人民解放军总医院第六医学中心62例支气管哮喘患者作为研究组,其中轻度急性发作27例,中度急性发作22例,重度急性发作13例。另收集同时期、同年龄段30例健康体检者作为对照组。采用实时荧光定量PCR（RT-PCR）检测各组血清miR-1165-3p、miR-145表达水平。采用Spearman相关分析不同程度支气管哮喘患者与血清miR-1165-3p、miR-145之间的相关性。通过受试者工作特征（ROC）分析血清miR-1165-3p、miR-145表达水平对不同程度支气管哮喘的诊断效能。结果：与对照组相比,研究组中白细胞介素-6（IL-6）、嗜酸性粒细胞、总免疫球蛋白E（IgE）水平显著升高,第1秒用力呼气容积（FEV₁）占预测值百分比（FEV₁%）则显著降低,差异均有统计学意义（P＜0.05）。不同严重程度支气管哮喘患者（轻度、中度、重度）血清miR-1165-3p、miR-145表达水平均高于健康对照组,支气管哮喘越严重,其表达水平越高,且组间、组内比较差异均有统计学意义（P＜0.05）。Spearman相关分析显示,miR-1165-3p、miR-145、IL-6表达水平与哮喘严重程度呈正相关（P＜0.05）,FEV₁%与哮喘严重程度呈负相关（P＜0.05）,嗜酸性粒细胞、总IgE与哮喘严重程度无相关性（P＞0.05）。对轻度、中度、重度急性支气管哮喘发作的诊断效能显示：血清miR-1165-3p的曲线下面积（AUC）（0.95CI）分别为3.085（0.326～29.221）、0.712（0.611～0.829）、0.755（0.602～0.948）。血清miR-145的AUC（0.95CI）分别为0.833（0.708～0.979）、0.754（0.590～0.964）、0.816（0.671～0.993）。结论：血清miR-1165-3p、miR-145表达水平具有较高的诊断效能,支气管哮喘越严重,诊断的特异性越高,可作为支气管哮喘严重程度的无创诊断指标。     

Dengue deaths in Puerto Rico: lessons learned from the 2007 epidemic

Background

The incidence and severity of dengue in Latin America has increased substantially in recent decades and data from Puerto Rico suggests an increase in severe cases. Successful clinical management of severe dengue requires early recognition and supportive care.

Methods

Fatal cases were identified among suspected dengue cases reported to two disease surveillance systems and from death certificates. To be included, fatal cases had to have specimen submitted for dengue diagnostic testing including nucleic acid amplification for dengue virus (DENV) in serum or tissue, immunohistochemical testing of tissue, and immunoassay detection of anti-DENV IgM from serum. Medical records from laboratory-positive dengue fatal case-patients were reviewed to identify possible determinants for death.

Results

Among 10,576 reported dengue cases, 40 suspect fatal cases were identified, of which 11 were laboratory-positive, 14 were laboratory-negative, and 15 laboratory-indeterminate. The median age of laboratory-positive case-patients was 26 years (range 5 months to 78 years), including five children aged <15 years; 7 sought medical care at least once prior to hospital admission, 9 were admitted to hospital and 2 died upon arrival. The nine hospitalized case-patients stayed a mean of 15 hours (range: 3–48 hours) in the emergency department (ED) before inpatient admission. Five of the nine case-patients received intravenous methylprednisolone and four received non-isotonic saline while in shock. Eight case-patients died in the hospital; five had their terminal event on the inpatient ward and six died during a weekend. Dengue was listed on the death certificate in only 5 instances.

Conclusions

During a dengue epidemic in an endemic area, none of the 11 laboratory-positive case-patients who died were managed according to current WHO Guidelines. Management issues identified in this case-series included failure to recognize warning signs for severe dengue and shock, prolonged ED stays, and infrequent patient monitoring.     

Apoptosis of pancreatic acinar cells in acute pancreatitis: is it good or bad?

Acute pancreatitis is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The events that regulate the severity of acute pancreatitis are, for the most part, unknown. Several recent studies have suggested that the acinar cell response to injury may be an important determinant of disease severity. In these studies, mild acute pancreatitis was found to be associated with extensive apoptotic acinar cell death while severe acute pancreatitis was found to involve extensive acinar cell necrosis but very little acinar cell apoptosis. These observations have led to the hypothesis that apoptosis might be a favorable response to acinar cell and that interventions which favor induction of apoptotic, as opposed to necrotic, acinar cell death might reduce the severity of an attack of acute pancreatitis. This review aims to discuss our current understanding of the contribution of acinar cell apoptosis to the severity of acute pancreatitis.     

Chlamydia pneumoniae-specific IgE is prevalent in asthma and is associated with disease severity

Background

Several Chlamydia pneumoniae (Cp) biomarkers have been associated with asthma but Cp-specific IgE (Cp IgE) has not been investigated extensively. Our objective was to investigate Cp IgE in community adult asthma patients.

Methods

(1) Prevalence of Cp IgE (measured by immunoblotting) and Cp DNA (by polymerase chain reaction) in peripheral blood, and biomarker associations with asthma severity. (2) Case-control studies of Cp IgE association with asthma using healthy blood donor (study 1) and non-asthmatic clinic patient (study 2) controls.

Results

Of 66 asthma subjects (mean age 40.9 years, range 5–75, 59% male, 45% ever-smokers) 33 (50%) were Cp IgE positive and 16 (24%) were Cp DNA positive (P = 0.001 for association of Cp IgE and DNA). Cp IgE was detected in 21% of mild intermittent asthma v 79% of severe persistent asthma (test for trend over severity categories, P = 0.002). Cp IgE detection was significantly (P = 0.001) associated with asthma when compared to healthy blood donor controls but not when compared to clinic controls.

Conclusions

Half of this sample of community asthma patients had detectable IgE against C. pneumoniae. Cp IgE was strongly and positively associated with asthma severity and with asthma when healthy blood donor controls were used. These results support the inclusion of Cp IgE as a biomarker in future studies of infectious contributions to asthma pathogenesis.     

National asthma attack audit 1991-2. General Practitioners in Asthma Group.

OBJECTIVE--To describe the frequency and characteristics of asthma attacks in the United Kingdom and to compare actual management with recommended guidelines for the management of attacks. DESIGN--Correspondence survey. SETTING--218 general practices in the United Kingdom. SUBJECTS--1775 patients of all ages who had a total of 1805 asthma attacks over three months. MAIN OUTCOME MEASURES--Patient characteristics, place of management of attacks, comparison of actual management with recommended guidelines. RESULTS--Of the 1805 attacks, 300 occurred in boys aged 0-9, 144 in girls aged 0-9, and 118 in women aged 20-29. The estimated frequency of attacks in the community was 14.3 per 1000 patients per year. 1546 (86%) patients with attacks were managed within general practice, 225 (12%) were admitted to hospital, and 34 (2%) were discharged from an accident and emergency department. Two patients died. On initial presentation, 248 (14%) patients were "not breathless," 900 (50%) were "moderately breathless," 535 (30%) were "breathless and distressed," 68 (4%) were "too breathless to talk," and 2 were "moribund." Recording of clinical data was variable. Underuse of nebulised bronchodilators and systemic steroid was apparent in all grades of clinical severity. Contrary to current guidelines for asthma management, "step up" in maintenance therapy after an attack was often not practised. CONCLUSION--Reported management was at variance with recommended guidelines. This has major implications for the design and distribution of future guidelines.     

Change of Cu,Zn-superoxide Dismutase Activity of Guinea Pig Lung in Experimental Asthma

Correlation between the level of reactive oxygen species (ROS) generated by airway inflammatory cells and superoxide dismutase (SOD) activity of pulmonary tissue during an asthma attach was investigated in a guinea pig model of allergic asthma. In addition, the influence of SOD inhibition by diethyldithiocarbamate (DDC, Cu-chelating agent) on the airway was investigated in terms of pulmonary function during an asthma attach. Relative to controls, the capacity of bronchoalveolar lavage fluid (BAL) cells to release ROS was significantly increased in guinea pigs sensitized with ovalbumin (OA) as the antigen, and significantly increased in guinea pigs with an asthma attack provoked by the inhalation of OA. SOD activity was increased significantly in the antigen-sensitized group. The asthma provocation group showed a tendency for increase in total SOD activity, compared with the sensitization group, whose increase was dependent on the increase in copper, zinc-SOD (Cu, Zn-SOD) activity. Pretreatment with DDC increased the severity and duration of the asthma attack. These results were indicated that Cu, Zn-SOD was closely involved in the asthma process, particularly in the scavenging of oxygen radicals secreted from BAL cells.