A recent increase in asthma mortality in the northwestern United States

Epidemiologic studies have suggested a recent increase in asthma mortality in New Zealand and the United States. Vital statistics were used to calculate asthma mortality rates for Washington and Oregon from 1972 through 1983, adjusting for the nosologic redefinition of asthma in 1979. Between 1977 and 1983, age-adjusted mortality from asthma increased 82% in these two states. The combined age-specific asthma mortality rates for Washington and Oregon showed that the increase was concentrated in the greater than or equal to 75 age group, in which mortality increased from 4.7 to 12.0 per 100,000 between 1977 and 1983. A significant increasing trend in the proportion of death certificates listing a cardiac dysrhythmia along with asthma as a cause of death was observed overall, in the State of Washington alone, and in decedents 75 or more years of age. The same trend was not statistically significant in Oregon or among younger decedents. This increase in asthma mortality may be due to a change in therapy such as an increased reliance on beta-agonists and theophylline preparations in combination, a change in the clinical definition of asthma, or other as yet unrecognized factors. Further investigation of these findings is warranted.     

Respiratory arrest in near-fatal asthma

BACKGROUND AND METHODS. The majority of asthma-related deaths occur outside the hospital, and therefore the exact factors leading to the terminal event are difficult to ascertain. To examine the mechanisms by which patients might die during acute exacerbations of asthma, we studied 10 such patients who arrived at the hospital in respiratory arrest or in whom it developed soon (within 20 minutes) after admission. RESULTS. The characteristics of the group were similar to those associated in the literature with a high risk of death from asthma, including a long history of the disease in young to middle-aged patients, previous life-threatening attacks or hospitalizations, delay in obtaining medical aid, and sudden onset of a rapidly progressive crisis. Extreme hypercapnia (mean [+/- SD] partial pressure of arterial carbon dioxide, 97.1 +/- 31.1 mm Hg) and acidosis (mean [+/- SD] pH, 7.01 +/- 0.11) were found before mechanical ventilation was begun, and four patients had hypokalemia on admission. Despite the severe respiratory acidosis, no patient had a serious cardiac arrhythmia during the resuscitation maneuvers or during hospitalization. We observed systemic hypertension and sinus tachycardia in eight patients, atrial fibrillation in one, and sinus bradycardia in another. In both patients with arrhythmia the heart reverted to sinus rhythm immediately after manual ventilation with 100 percent oxygen was begun. The median duration of mechanical ventilation was 12 hours, and all patients had normocapnia on discharge from the hospital. CONCLUSIONS. We conclude that at least in this group of patients, the near-fatal nature of the exacerbations was the result of severe asphyxia rather than cardiac arrhythmias. These results suggest that undertreatment rather than overtreatment may contribute to an increase in mortality from asthma.     

Asthma death among adults in Japan 1995-1997. Analysis of 295 cases reported questionnaires sent to hospitals with more than 100 beds. Asthma Death Investigation Committee]

To clarify recent trends in adult asthma mortality, the Asthma Death Investigation Committee of Japan studied the clinical characteristics of 295 patients who died of asthma between 1995 and 1997. Males were slightly more than females among the death cases. Approximately half of the patients ranged in age from 60 to 79 years. Tendency to increase of death among young male adults continued. One third of the patient deaths involved the asphyxic type, while status asthmaticus was the cause death in 21.9%. Half of the asthmatics died in hospitals or emergency rooms, and places where the fatal attacks occurred were mainly patients' houses. The main cause fatal asthma attacks was respiratory infection, followed by fatigue, stress, and discontinuation of medication. Most of the patients were classified moderate or severe type of asthma 1 month before death. Histories of life-threatening attacks and hospitalization due to severe attacks, irregular visits to the hospital, low compliance, and insufficiency of corticosteroid treatment were suggested as the main risk factors in adult asthma deaths.     

Risk factors for death in adults with severe asthma

BACKGROUND: Mortality risk in adult asthma is poorly understood, especially the interplay among race, disease severity, and health care access. OBJECTIVE: To examine mortality risk factors in adult asthma. METHODS: In a prospective cohort study of 865 adults with severe asthma in a closed-panel managed care organization, we used structured interviews to evaluate baseline sociodemographics, asthma history, and health status. Patients were followed up until death or the end of the study (mean, 2 years). We used Cox proportional hazards regression to evaluate the impact of sociodemographics, cigarette smoking, and validated measures of perceived asthma control, physical health status, and severity of asthma on the risk of death. RESULTS: We confirmed 123 deaths (mortality rate, 6.7 per 100 person-years). In an analysis adjusted for sociodemographics and tobacco history, higher severity-of-asthma scores (hazard ratio [HR], 1.11 per 0.5-SD increase in severity-of-asthma score; 95% confidence interval [CI], 1.01-1.23) and lower perceived asthma control scores (HR, 0.91 per 0.5-SD increase in perceived asthma control score; 95% CI, 0.83-0.99) were each associated with risk of all-cause mortality. In the same adjusted analysis, African American race was not associated with increased mortality risk relative to white race (HR, 0.64; 95% CI, 0.36-1.14). CONCLUSIONS: In a large managed care organization in which access to care is unlikely to vary widely, greater severity-of-asthma scores and poorer perceived asthma control scores are each associated with increased mortality risk in adults with severe asthma, but African American patients are not at increased risk for death relative to white patients.     

Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma.

BACKGROUND: Little is known about the morbidity and mortality among older adults with asthma requiring hospital care. OBJECTIVES: To determine whether an initial hospital visit for asthma was associated with an increase in use of inhaled corticosteroids (CCS) at discharge, and to identify risk factors for recurrent asthma hospital visits and death. METHODS: A retrospective cohort analysis identified 93,174 persons 65 years and older enrolled in the Tennessee Medicaid program for at least 1 year and free of asthma hospital visits during that year; 510 survived a single hospital visit for asthma in 1992 and comprised the study population. Main outcome measures included recurrent hospital visit for asthma and all-cause mortality during the year after an asthma hospital visit. RESULTS: Among the 510 study subjects, 10% were on inhaled CCS at admission compared with 11% at discharge. Twenty-three percent of the population had recurrent asthma hospital visits and 12% died during 1-year followup. Asthma severity was the strongest independent risk factor for both a recurrent hospital visit [relative risk for moderate to severe disease 1.92 (1.01 to 3.66), and for near-fatal disease 2.28 (1.01 to 5.13), respectively] and death [relative risk for moderate to severe disease 2.99 (1.07 to 8.32) and for near-fatal disease 4.44 (1.34 to 4.69), respectively]. CONCLUSIONS: In this population, older adults with an exacerbation of asthma requiring hospital care experienced significant morbidity and mortality. An acute hospital visit for an asthma exacerbation did not result in initiation of inhaled CCS therapy. Asthma severity predicted both recurrent hospital visits and all-cause mortality among older adults with asthma requiring hospital care.     

Placebo-controlled double-blind food challenge in asthma

To determine the prevalence of food allergy as a cause of exacerbation of asthma, we studied 300 consecutive patients with asthma (7 months to 80 years of age) who attended a respiratory clinic. Each patient was screened for possible food allergy by means of a questionnaire and by skin prick tests with the six food allergens most common in our area. Patients with either a suggestive history and/or a positive prick test and/or RAST underwent double-blind food challenge with lyophilized food in capsules or food mixed in a broth to disguise its taste. Pulmonary function tests and symptoms were followed for 8 hours after each challenge. Of the 300 patients screened, only 25 had either a history or skin prick tests or RAST responses suggestive of food allergy. Twenty patients had interpretable food challenges. In these 20 patients, food challenge caused asthma in six and caused other symptoms (atopic dermatitis and gastrointestinal symptoms) in five. On rechallenge after pretreatment with disodium cromoglycate (300 mg 30 minutes before the food challenge), the asthmatic response was blocked in four of five subjects. The patients with asthma with food allergy were generally young, had a current or past history of atopic dermatitis, and high total serum IgE levels. Our findings confirm that food allergy can elicit asthma, but its incidence is low, even in the population attending a specialty clinic. Food elimination diets should not be prescribed for all patients reporting an adverse reaction to foods or having a positive skin prick test and/or RAST with food allergens. In patients with asthma caused by food allergy, disodium cromoglycate may be used to complement elimination diets.     

Mortality for liver disease in patients with HIV infection: a cohort study

We undertook this study to assess the association between the various potential causes of liver disease in HIV-seropositive patients and mortality due to liver failure. Three hundred and eight in-hospital deaths were observed from 1987 to December 1995 in a prospectively followed cohort of 1894 HIV-seropositive patients. For each study subject, clinical data were evaluated to assess whether liver failure had substantially contributed to mortality. A case control study nested in the cohort was then performed, which compared demographic and clinical variables observed at enrollment and during follow-up between patients who died for liver disease as the main or concurrent cause of death (cases) and those who died as a result of illness related to AIDS or other causes (controls). Among 308 in-hospital deaths, liver failure was found the cause of death in 35 patients (12%); in 16 cases, it was the primary cause and in 19 cases it was concurrent. Multivariate analysis showed that in-hospital liver-disease-related mortality was independently associated with hepatitis B surface antigen reactivity (odds ratio [OR], 9; 95% confidence interval [CI], 3.8-21.7) and history of alcohol abuse (OR, 2.3; 95% CI, 1-5.2). Prevention and treatment of hepatitis B virus infection and alcohol intake are management priorities in HIV-seropositive patients.     

Contribution of malformations and genetic disorders to mortality in a children's hospital

Malformations and genetic disorders are the leading cause of infant mortality in the US. Many malformations have a genetic basis due to genic, chromosomal, or multifactorial causation. We have studied the proportion of pediatric cases in a university-affiliated children's hospital that died of malformations and genetic disorders. We reviewed, retrospectively, deaths over a 4 year period (1994-1998) at Primary Children's Medical Center (PCMC), a university-affiliated tertiary children's referral hospital in Utah. The age at death and the cause of death were recorded for each case. We analyzed 523 cases; 180 (34.4%) deaths were due to malformations and genetic disorders. Of those 180, 30 (16.7%) had chromosome anomalies, 21 (11.7%) had a recognizable malformation syndrome, 118 (65.6%) had a malformation of unknown cause, and 11 (6.1%) had some other genetic disorder. One hundred and twenty-two (23.3%) deaths were due to trauma (accidental and non-accidental). Seventy-nine (15.1%) deaths were due to short gestation or perinatal complications. Forty-five (8.6%) deaths were due to an infectious disease and 45 (8.6%) from neoplasms. Thirteen (2.5%) were diagnosed for sudden infant death "syndrome." Twelve (2.3%) patients with malformations and/or genetic disorders died of an acquired condition not clearly related to the underlying disorder. Seven (1.3%) patients died of an unknown cause and 20 (3.8%) patients died of other specified conditions. In addition, 51.0% patients (age <1 year) died of a malformation and/or genetic disorder. Genetic disorders and malformations are a substantial cause of mortality in a referral pediatric hospital. Knowledge of the impact of genetic diseases on mortality is important for the integration of preventive measures and health care strategies to care effectively for patients and their families. This information emphasizes the importance of further study of whether or not early recognition influences mortality rate and management.     

The use of beta-agonists and the risk of death and near death from asthma.

BACKGROUND. Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS. Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS. The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS. An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.     

Persistent peripheral airway obstruction in children with severe asthma

We reviewed pulmonary function data on 447 children with the diagnosis of asthma, who were studied in our laboratory over a 6-year interval. We found 19 with evidence of consistent airway obstruction. Two patients who had obvious causes for persistent obstruction were excluded. Seven of the remaining 17 patients consented to further studies. In six of the seven patients studied, flow rates at low lung volumes were severely depressed and remained unchanged after 2 weeks of vigorous "inpatient" therapy. No clinical benefit was apparent. One patient had relentlessly worse disease and died of his asthma. The autopsy revealed changes characteristic of asthma. We conclude that some children with severe asthma have persistent and severe peripheral airway obstruction. These findings challenge the current paradigm that asthma in children is a completely "reversible" illness. Long-term follow-up of children with persistent chronic obstruction may clarify the question of childhood origin of adult lung disease.     

Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic.

BACKGROUND: Depressive symptoms are associated with noncompliance and even sudden death in asthma patients. Some studies suggest that low-income, minority, inner-city asthma patients may be at high risk for asthma-related morbidity and mortality in which depression may be a risk factor. Minimal data are available on the prevalence of depression and other mood disorders in asthma patients. OBJECTIVE: In this pilot study, we examined the prevalence of depression and the association between depression and measures of asthma severity in patients at an inner-city asthma clinic. METHODS: Mood disorders were diagnosed using a diagnostic interview given to patients (N = 44) at asthma clinic visits. Inhaled steroid dose, FEV1 percentage, and asthma severity were also obtained. RESULTS: Eighteen patients (41%) had a lifetime mood disorder but only seven of these patients received pharmacotherapy. Patients with a past mood disorder had significantly higher FEV1 percentage predicted values (P = 0.03) than those without a mood disorder. Trends toward less severe asthma (P = 0.13) and lower inhaled steroid dose (P = 0.13) in patients with a mood disorder history were also found. CONCLUSIONS: The data suggest that mood disorders are common, but often unrecognized and untreated in asthma patients. The data also suggest that mood disorders are not necessarily associated with more severe asthma, at least in the population studied.     

Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab.

Adenoviruses are emerging as a major cause of infectious complications after allogeneic transplantation. We evaluated the incidence and outcome of symptomatic adenovirus infection or adenovirus disease after alemtuzumab-based reduced-intensity conditioning in 86 consecutive patients. The overall probability of adenovirus disease was 18.4% (11/86 patients). Five patients died of progressive adenovirus disease, and this was the most important infectious cause of mortality in this cohort. The probability of nonrelapse mortality was 49% in patients with adenovirus disease compared with 25.5% in those without (P=.007). The severity of lymphocytopenia and continuation of immunosuppressive therapy were the most important risk factors for progressive adenovirus disease and death. In contrast, patients who were not receiving immunosuppressive therapy or had had it reduced or withdrawn cleared the virus. We also detected a correlation between the lack of preemptive anti-cytomegalovirus (CMV) therapy for CMV reactivation and the risk of progressive adenovirus disease (P=.05). Our findings highlight the emergence of adenovirus as an important posttransplantation pathogen even after reduced-intensity conditioning and demonstrate the effect of the severity of lymphocytopenia, anti-CMV prophylaxis, and immunosuppressive therapy on the outcome of adenovirus disease.     

Five-year mortality in lithium-treated manic-depressive patients.

A hundred and thirty-three affective disorder patients who received prophylactic treatment with lithium were followed prospectively for 5 years and their mortality was recorded. Twenty-two patients died during the period, 13 from natural causes and nine from definite or probable suicide. The observed mortality was significantly greater than the expected overall, and also when natural causes and suicide were considered independently. No patients died from lithium intoxication or lithium-induced side effects. Patients who died from suicide were all bipolars or suffered from affective disorder with uncertain polarity. They were significantly younger than the patients who died from natural causes, they tended to lead isolated lives and they suffered a violent death. The older patients who died from natural causes had often had physical illness and alcohol abuse prior to the start of lithium treatment. The results of the study speak in favour of the establishment of comprehensive treatment programmes possibly in the framework of specialised affective disorder clinics.     

The challenge of mild persistent asthma.

OBJECTIVE: To review the current data and treatment options for mild persistent asthma. DATA SOURCES: A MEDLINE search was performed for relevant articles. STUDY SELECTION: The expert opinion of the author was used to select studies for inclusion in this review. RESULTS: Current data suggest that asthma severity is determined early in life and that disease progression may not occur outside early childhood. Furthermore, no therapy has been demonstrated to clearly prevent or reverse structural airway changes in patients with persistent asthma. Thus, the primary goal of asthma therapy is to prevent disease exacerbations rather than to halt disease progress, at least in patients past early childhood. Published reports of severe exacerbations in patients with reported mild asthma may actually reflect inclusion of patients with more severe forms of the disease who were inappropriately classified in terms of asthma severity. CONCLUSION: Unlike the case for moderate and severe asthma, where regular therapy with inhaled corticosteroids is clearly the treatment of choice, clear guidelines for treating patients with mild persistent asthma have not been established. Patients with mild disease without severe exacerbations may require only the minimum therapy necessary for disease control.     

Cause‐specific long‐term mortality rates in patients recovered from community‐acquired pneumonia as compared with the general Dutch population

Insights into long‐term mortality, especially into the cause of death after initial recovery from an episode of community‐acquired pneumonia (CAP), may help in determining optimal preventive measures in such patients. Prospective observational cohort studies were conducted to compare cause‐specific long‐term mortality rates for 356 patients who had recovered from CAP with those of the general Dutch population (16.3 million) between 2003 and 2007. The Dutch Municipal Public Records Database and death certificates were used to determine cause‐specific mortality rates up to 7 years after discharge. In patients who had recovered from CAP, cumulative 1‐year, 5‐year and 7‐year mortality rates were 17%, 43% and 53%, respectively, as compared with 4%, 19% and 24% for an age‐matched and sex‐matched population reference cohort. Overall, patients who had recovered from CAP had significantly higher long‐term mortality than matched population controls (rate ratio (RR) 3.6; p <0.001). In the years after an episode of CAP, malignancy (27%), chronic obstructive pulmonary disease (COPD) (19%) and cardiovascular disease (16%) were the most frequent causes of death. Only 6% died of pneumonia, as compared with 3.2% in the general population. After initial recovery from an episode of CAP, long‐term mortality rates are more than three times as high as in the general population. The causes of long‐term mortality were mostly comorbidity‐related, and significantly different from those in the general population. After an episode of CAP, optimization of treatment of comorbidities, such as treatment for COPD, might improve long‐term survival rates.     

Asthma deaths during sports: report of a 7-year experience

BACKGROUND: Asthma mortality and the mortality of athletes during sports have been described separately in detail in the medical literature. However, asthma has not been reported as a cause of death in competitive athletes. OBJECTIVE: The object of this study was to raise the awareness of physicians, coaches, trainers, and parents that children and adults can have fatal asthma exacerbations during and immediately after participating in sports. METHODS: The Temple Sports Asthma Research Center identified athletes from 1993 until 2000 who died during or after sporting activity by using the nationwide Burrell's Information Service. Once a possible asthma-related sports death was identified, the autopsy report was requested from the coroner or medical examiner, and an attempt was made to contact the family. Contact with the family was limited to information about the death, medical history, sports involvement, and any medication usage by the person who had died. Secondary sources, including news reports, were used to confirm whether the subject died of asthma during or immediately after a sporting activity. RESULTS: Two hundred sixty-three possible cases were identified. Sixty-one deaths met the criteria for study inclusion. White deaths outnumbered black deaths by 2 to 1. Deaths among male subjects predominated. Most subjects were younger than the age of 20 years, with the most prevalent age group being between 10 to 14 years old. Fifty-one percent (18 of 35) of the competitive athletes had their fatal event while participating in organized sport, 14 in a practice situation and 4 deaths during a game or meet setting. Basketball and track were the 2 most frequent activities performed at the time of the fatal event. CONCLUSION: The subjects who had fatal asthma exacerbations were usually white male subjects between the ages of 10 and 20 years. Mild intermittent or persistent asthma by history was commonly identified. Sudden fatal asthma exacerbations occur in both competitive and recreational athletes and can be precipitated by sporting activity.     

Prognosis of intractable asthma]

Forty-nine intractable asthma patients from January 1981 were divided into three groups. Group I consisted of patients still alive after ten years (January 1991) who were receiving decreased doses of steroids or no steroids at all. Group II patients were also alive, but the doses of steroids they were receiving were unchanged. Group III consisted of patients who had died during the ten years. Of the 49 patients, nine were in Group I, 13 in Group II and 17 in Group III. The condition of the other 10 patients was unknown. The mortality rate of the known 39 patients over 10 years was 43.6%, a very high rate. The groups of living patients (I + II) were younger than the patients in the dead group (III) and the latter patients had more obstructive ventilatory dysfunction in the stable state (FEV1.0/FVC%, and %FEV1.0 were 56.1% and 52.8%) in 1980. In the therapy carried out over the 10 years, antiallergic drugs and inhaled steroids were administered in order to decrease oral steroids in both Group I, II and III. In Group I, however, more patients had received immunotherapy (hyposensitization) or gold therapy than in Group II and III. There were more complications due to steroids during the ten years in Group II and III than in Group I. Aging and obstructive ventilatory dysfunction may be factors which worsen the prognosis of intractable asthma, and decreasing of the doses of oral steroids may be important to prevent complications.