Identifying patients at risk for fatal asthma
- J Mark Madison, MD
J Mark Madison, MD
- Professor of Medicine and Microbiology and Physiological Systems
- University of Massachusetts Medical School
- Richard S Irwin, MD
Richard S Irwin, MD
- Professor of Medicine
- University of Massachusetts Medical School
Assessing patient risk for a future fatal asthma exacerbation is important because many, if not most, asthma-related deaths are preventable if risk factors are recognized and addressed early .
The epidemiology and risk factors for fatal asthma are reviewed here. The evaluation and management of severe asthma are discussed separately. (See "Evaluation of severe asthma in adolescents and adults" and "Treatment of severe asthma in adolescents and adults".)
Asthma ranks 32nd as a cause of death worldwide, but mortality varies among and within countries [2,3]. Based on World Health Organization (WHO) data, age standardized death rates per 100,000 range from 46.56 in New Guinea, 17.16 in India, 1.65 in China, 1.62 in Russia, 0.97 in the United Kingdom, 0.88 in the United States, 0.82 in France, and 0.24 in the Netherlands .
In an analysis of the WHO database using a locally weighted scatter plot smoother (LOESS) curve for the 5 to 34-year age group weighted by the individual country population, asthma mortality was essentially unchanged from 2006 to 2012, after decreasing substantially from 1993 to 2006 . The analysis included the 46 countries for which data were available. The decline in death rates from 1993 to 2006 is largely attributable to the widespread use of inhaled glucocorticoids for persistent asthma and avoidance of highly potent, poorly selective beta-agonists such as isoprenaline forte and fenoterol .
Similar to international trends, asthma mortality in the United States has declined since reaching a peak in the 1990s (figure 1) . From 2001 to 2015, United States deaths due to asthma decreased from 15 deaths per million population to 10.3 deaths per million population [6,7]. Among individuals with asthma, the rate of asthma deaths decreased from 2.1 per 10,000 persons in 2001 to 1.4 per 10,000 persons in 2009 .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Royal College of Physicians. Why asthma still kills: National Review of Asthma Deaths (NRAD). http://www.rcplondon.ac.uk/sites/default/files/why-asthma-still-kills-full-report.pdf (Accessed on May 16, 2014).
- www.worldlifeexpectancy.com/cause-of-death/asthma/by-country (Accessed on September 22, 2017).
- Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, et al. Trends and Patterns of Differences in Chronic Respiratory Disease Mortality Among US Counties, 1980-2014. JAMA 2017; 318:1136.
- Ebmeier S, Thayabaran D, Braithwaite I, et al. Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993-2012). Lancet 2017; 390:935.
- Moorman JE, Rudd RA, Johnson CA, et al. National surveillance for asthma--United States, 1980-2004. MMWR Surveill Summ 2007; 56:1.
- Moorman JE, Akinbami LJ, Bailey CM, et al. National surveillance of asthma: United States, 2001-2010. Vital Health Stat 3 2012; :1.
- https://www.cdc.gov/asthma/most_recent_data.htm (Accessed on September 22, 2017).
- Sekiya K, Nakatani E, Fukutomi Y, et al. Severe or life-threatening asthma exacerbation: patient heterogeneity identified by cluster analysis. Clin Exp Allergy 2016; 46:1043.
- Romagnoli M, Caramori G, Braccioni F, et al. Near-fatal asthma phenotype in the ENFUMOSA Cohort. Clin Exp Allergy 2007; 37:552.
- Restrepo RD, Peters J. Near-fatal asthma: recognition and management. Curr Opin Pulm Med 2008; 14:13.
- Yii ACA, Tan JHY, Lapperre TS, et al. Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma. Allergy 2017.
- Eisner MD, Katz PP, Yelin EH, et al. Risk factors for hospitalization among adults with asthma: the influence of sociodemographic factors and asthma severity. Respir Res 2001; 2:53.
- Krishnan V, Diette GB, Rand CS, et al. Mortality in patients hospitalized for asthma exacerbations in the United States. Am J Respir Crit Care Med 2006; 174:633.
- Ali Z, Dirks CG, Ulrik CS. Long-term mortality among adults with asthma: a 25-year follow-up of 1,075 outpatients with asthma. Chest 2013; 143:1649.
- Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med 2005; 172:149.
- Ramnath VR, Clark S, Camargo CA Jr. Multicenter study of clinical features of sudden-onset versus slower-onset asthma exacerbations requiring hospitalization. Respir Care 2007; 52:1013.
- de Magalhães Simões S, dos Santos MA, da Silva Oliveira M, et al. Inflammatory cell mapping of the respiratory tract in fatal asthma. Clin Exp Allergy 2005; 35:602.
- DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol 1960; 13:27.
- James AL, Elliot JG, Abramson MJ, Walters EH. Time to death, airway wall inflammation and remodelling in fatal asthma. Eur Respir J 2005; 26:429.
- McFadden ER Jr, Warren EL. Observations on asthma mortality. Ann Intern Med 1997; 127:142.
- Turner MO, Noertjojo K, Vedal S, et al. Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med 1998; 157:1804.
- Kolbe J, Fergusson W, Garrett J. Rapid onset asthma: a severe but uncommon manifestation. Thorax 1998; 53:241.
- Rodrigo GJ, Rodrigo C. Rapid-onset asthma attack: a prospective cohort study about characteristics and response to emergency department treatment. Chest 2000; 118:1547.
- Plaza V, Serrano J, Picado C, et al. Frequency and clinical characteristics of rapid-onset fatal and near-fatal asthma. Eur Respir J 2002; 19:846.
- Reid LM. The presence or absence of bronchial mucus in fatal asthma. J Allergy Clin Immunol 1987; 80:415.
- Sur S, Crotty TB, Kephart GM, et al. Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? Am Rev Respir Dis 1993; 148:713.
- Perskvist N, Edston E. Differential accumulation of pulmonary and cardiac mast cell-subsets and eosinophils between fatal anaphylaxis and asthma death: a postmortem comparative study. Forensic Sci Int 2007; 169:43.
- Eisner MD, Lieu TA, Chi F, et al. Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma. Eur Respir J 2001; 17:233.
- Malmström K, Kaila M, Kajosaari M, et al. Fatal asthma in Finnish children and adolescents 1976-1998: validity of death certificates and a clinical description. Pediatr Pulmonol 2007; 42:210.
- Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2015. http://www.ginasthma.org/ (Accessed on May 23, 2015).
- Dhuper S, Maggiore D, Chung V, Shim C. Profile of near-fatal asthma in an inner-city hospital. Chest 2003; 124:1880.
- Mitchell I, Tough SC, Semple LK, et al. Near-fatal asthma: a population-based study of risk factors. Chest 2002; 121:1407.
- Marquette CH, Saulnier F, Leroy O, et al. Long-term prognosis of near-fatal asthma. A 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992; 146:76.
- Goeman DP, Abramson MJ, McCarthy EA, et al. Asthma mortality in Australia in the 21st century: a case series analysis. BMJ Open 2013; 3.
- Bush RK, Prochnau JJ. Alternaria-induced asthma. J Allergy Clin Immunol 2004; 113:227.
- Osborne ML, Pedula KL, O'Hollaren M, et al. Assessing future need for acute care in adult asthmatics: the Profile of Asthma Risk Study: a prospective health maintenance organization-based study. Chest 2007; 132:1151.
- Pumphrey RS, Gowland MH. Further fatal allergic reactions to food in the United Kingdom, 1999-2006. J Allergy Clin Immunol 2007; 119:1018.
- Roberts G, Patel N, Levi-Schaffer F, et al. Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study. J Allergy Clin Immunol 2003; 112:168.
- Yoshimine F, Hasegawa T, Suzuki E, et al. Contribution of aspirin-intolerant asthma to near fatal asthma based on a questionnaire survey in Niigata Prefecture, Japan. Respirology 2005; 10:477.
- Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience. J Allergy Clin Immunol 2004; 113:264.
- Fregonese L, Swan FJ, van Schadewijk A, et al. Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal asthma. J Allergy Clin Immunol 2005; 115:1148.
- Weir TD, Mallek N, Sandford AJ, et al. beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma. Am J Respir Crit Care Med 1998; 158:787.
- Levine M, Iliescu ME, Margellos-Anast H, et al. The effects of cocaine and heroin use on intubation rates and hospital utilization in patients with acute asthma exacerbations. Chest 2005; 128:1951.
- Krantz AJ, Hershow RC, Prachand N, et al. Heroin insufflation as a trigger for patients with life-threatening asthma. Chest 2003; 123:510.
- Martinez-Moragón E, Plaza V, Serrano J, et al. Near-fatal asthma related to menstruation. J Allergy Clin Immunol 2004; 113:242.
- Tan WC, Xiang X, Qiu D, et al. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease. Am J Med 2003; 115:272.
- Strunk RC. Identification of the fatality-prone subject with asthma. J Allergy Clin Immunol 1989; 83:477.
- Strunk RC. Death due to asthma. New insights into sudden unexpected deaths, but the focus remains on prevention. Am Rev Respir Dis 1993; 148:550.
- Barr RG, Woodruff PG, Clark S, Camargo CA Jr. Sudden-onset asthma exacerbations: clinical features, response to therapy, and 2-week follow-up. Multicenter Airway Research Collaboration (MARC) investigators. Eur Respir J 2000; 15:266.
- Watson L, Turk F, James P, Holgate ST. Factors associated with mortality after an asthma admission: a national United Kingdom database analysis. Respir Med 2007; 101:1659.
- Tsai CL, Lee WY, Hanania NA, Camargo CA Jr. Age-related differences in clinical outcomes for acute asthma in the United States, 2006-2008. J Allergy Clin Immunol 2012; 129:1252.
- Gelb AF, Schein A, Nussbaum E, et al. Risk factors for near-fatal asthma. Chest 2004; 126:1138.
- Kitch BT, Paltiel AD, Kuntz KM, et al. A single measure of FEV1 is associated with risk of asthma attacks in long-term follow-up. Chest 2004; 126:1875.
- Boushey H, Enright P. Spirometry enhances identification of high-risk patients with asthma. Chest 2007; 132:1112.
- Fuhlbrigge AL, Kitch BT, Paltiel AD, et al. FEV(1) is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol 2001; 107:61.
- Miller MK, Lee JH, Blanc PD, et al. TENOR risk score predicts healthcare in adults with severe or difficult-to-treat asthma. Eur Respir J 2006; 28:1145.
- Sorkness RL, Bleecker ER, Busse WW, et al. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation. J Appl Physiol (1985) 2008; 104:394.
- Kikuchi Y, Okabe S, Tamura G, et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med 1994; 330:1329.
- Bijl-Hofland ID, Cloosterman SG, Folgering HT, et al. Relation of the perception of airway obstruction to the severity of asthma. Thorax 1999; 54:15.
- Serrano J, Plaza V, Sureda B, et al. Alexithymia: a relevant psychological variable in near-fatal asthma. Eur Respir J 2006; 28:296.
- Ruffin RE, Latimer KM, Schembri DA. Longitudinal study of near fatal asthma. Chest 1991; 99:77.
- Motomura C, Odajima H, Tezuka J, et al. Perception of dyspnea during acetylcholine-induced bronchoconstriction in asthmatic children. Ann Allergy Asthma Immunol 2009; 102:121.
- Magadle R, Berar-Yanay N, Weiner P. The risk of hospitalization and near-fatal and fatal asthma in relation to the perception of dyspnea. Chest 2002; 121:329.
- Barreiro E, Gea J, Sanjuás C, et al. Dyspnoea at rest and at the end of different exercises in patients with near-fatal asthma. Eur Respir J 2004; 24:219.
- Nannini LJ, Zaietta GA, Guerrera AJ, et al. Breath-holding test in subjects with near-fatal asthma. A new index for dyspnea perception. Respir Med 2007; 101:246.
- George MR, O'Dowd LC, Martin I, et al. A comprehensive educational program improves clinical outcome measures in inner-city patients with asthma. Arch Intern Med 1999; 159:1710.
- Cowie RL, Revitt SG, Underwood MF, Field SK. The effect of a peak flow-based action plan in the prevention of exacerbations of asthma. Chest 1997; 112:1534.
- MORTALITY STATISTICS
- CLINICOPATHOPHYSIOLOGICAL PROFILES
- Slow onset fatal asthma
- Rapid onset fatal asthma
- IDENTIFYING HIGH-RISK PATIENTS
- Major risk factors
- Minor risk factors
- Objective measures
- Poor perception of dyspnea
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS