Long-term Mortality Among Adults With Asthma A 25-Year Follow-up of 1,075 Outpatients With Asthma Zarqa Ali, MD; Christina Glattre Dirks, MD, PhD; and Charlotte Suppli Ulrik, MD, DMSc R1 정수웅 Chest 2013;143(6):

 Patients with severe or uncontrolled asthma have a poorer prognosis regarding lung function decline and a higher risk of mortality.  A decline in asthma mortality has been observed over past decades, probably due to an increased use of inhaled corticosteroids.  Several risk factors of asthma mortality Frequent use of rescue medication Low use of inhaled corticosteroid Need for treatment with systemic corticosteroid or theophylline Frequent asthma attack Hospitalization for asthma Reduced lung function Introduction

 A prospective study of 1,148 subjects with asthma revealed that monitoring peak expiratory flow (PEF) and FVC substantially reduced mortality.  Our knowledge of the long-term mortality in patients with asthma is still limited.  The aim of our study Analysis of longterm mortality among adults with well-characterized asthma Identification of long-term risk factors for subsequent death from asthma Introduction

 Study Group Method Attacks of breathlessness, wheezing, or both Chest tightness and dry cough Typical history of asthma FEV1 after - FEV1 before/ FEV1 before > 15% after a standard dose of inhaled β 2-agonist, oral corticosteroid, or both Reversibility of FEV1 Highest – Lowest measurement / mean of measurements > 20% Diurnal variability in PEF rate Nonallergic asthma At the time of referral, patients were tested for as follows History taking IgE concentration skin prick tests Radioallergosorbent tests bronchial provocation tests allergic asthma Consecutive subjects (>15 years of age) referred by general practitioners to the Allergy and Chest Clinic at Frederiksberg Hospital, Copenhagen, because of known or suspected asthma during the years 1974 to At least 2 of following criteria

 Control subjects matched for age, sex, and year of referral Control subjects were randomly selected from all subjects who attended the clinic for suspected or known allergic diseases other than asthma, including allergic and nonallergic rhinitis, atopic dermatitis, and urticaria. Method

At the time of enrollment, patients were asked or tested for as follows Known allergies Disposition to allergic diseases Allergic symptoms (rhinitis,eczema, and urticaria) Duration and frequency of respiratory symptoms Triggering factors Use of antiasthma medication Numbers of previous ED visits Hospital admission for asthma A detailed history taking

At the time of enrollment, patients were asked or tested for as follows Serum total IgE by PRIST The standard skin prick test using the following inhalation allergen (birth, grass, mug wort, horse, dog, cat, house dust mite, molds) Allergen speicific IgE by aluminum radioallergosorbent tests Bronchial provocation tests Blood eosinophilic count Tests for IgE-mediated allergy

At the time of enrollment, patients were asked or tested for as follows FEV1,PEF,FVC by using a dry-wedge bellows spirometer The evaluation of reversibility by using inhalation of a standard dose of a short acting β 2-agonist Spirometric tests

All patients were enrolled at the first visit (during the years 1974 to 1990), and were followed up until the end of Information about deaths was obtained from the Danish Death Register and from the Danish National Board of Health. Causes of death were classified into five categories, according to the ICD-10 Information concerning current status (dead or alive) at the end of follow-up (2011) was obtained for all asthmatic case subjects (n =1,075; 425 men) and control subjects (n=1,075; 425 male) Mortality Status asthmaticus Obstructive lung disease not classified as status asthmaticus, Cardiovascular disease Malignant neoplasm Other causes

Result

Mean age : 38.0 years The mean follow-up period : 25.6 years (SD, 4.2)

(RR, 2.1; 95% CI, ; P,.001) The excess mortality among asthma cases was explained, to a large extent, by death caused by obstructive lung disease

No statistically significant differences in baseline characteristics between the patients who died of status asthmaticus (n=20) and the patients classified as dying from obstructive lung disease (n=75)

No significant association between smoking habits at the time of enrollment and subsequent risk of death from asthma. No significant association between self-reported severity of symptoms and risk of subsequent death from asthma.

Significant association between nonallergic asthma and subsequent death from asthma was explained primarily by the fact that the patients with nonallergic asthma were older and had a lower level of lung function at the time of enrollment compared with the patients with extrinsic asthma.

 This 25-year prospective study showed that mortality from asthma is still a matter of concern.  Not only did our study show an excess of all-cause mortality among patients with asthma compared with an age- and sex-matched control group.  More importantly, it also showed that the excess mortality was primarily due to death from asthma and obstructive lung disease not classified as status asthmaticus. Discussion

May some of them have died of smoking related obstructive lung disease ?? Patients in the current study had asthma diagnosed by objective criteria, and furthermore, 65% of the enrolled subjects with asthma were life-long never smokers. We are, therefore, confident that the cause of death in the majority of these patients was asthma, if not all. Discussion

Asthma case subjects who later died of status asthmaticus or obstructive lung disease not classified as status asthmaticus have the following characteristics A longer duration of asthma a longer period of time with poorly controlled asthma due to lack of controller therapy Older than the remaining case subjects (n=980) A lower level of FEV 1 A lower FEV 1 /FVC ratio A higher degree of bronchodilator reversibility A higher peripheral blood eosinophil count No significant association between smoking and risk of subsequent death from asthma Discussion more severe asthma more difficult to control asthma

People with well-characterized asthma have an excess mortality, primarily due to asthma. Subsequent death from asthma was not only associated with age and level of lung function, but also with degree of bronchodilator reversibility, peripheral blood eosinophil count, and previous acute hospital contacts for asthma Conclusion