NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity
Corresponding Author
D. R. Morales
Quality, Safety & Informatics Group, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Correspondence
Dr. Daniel R Morales, Quality, Safety & Informatics Group, Medical Research Institute, University of Dundee, Mackenzie Building, Dundee DD2 4BF, UK.
Tel.: +44-1382-383706
Fax: +44(0)1382383802
E-mail: [email protected]
Search for more papers by this authorB. Guthrie
Quality, Safety & Informatics Group, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorB. J. Lipworth
Scottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorC. Jackson
School of Medicine, University of Central Lancashire, Preston, UK
Search for more papers by this authorP. T. Donnan
Dundee Epidemiology and Biostatistics Unit, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorV. H. Santiago
Quality, Safety & Informatics Group, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorCorresponding Author
D. R. Morales
Quality, Safety & Informatics Group, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Correspondence
Dr. Daniel R Morales, Quality, Safety & Informatics Group, Medical Research Institute, University of Dundee, Mackenzie Building, Dundee DD2 4BF, UK.
Tel.: +44-1382-383706
Fax: +44(0)1382383802
E-mail: [email protected]
Search for more papers by this authorB. Guthrie
Quality, Safety & Informatics Group, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorB. J. Lipworth
Scottish Centre for Respiratory Research, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorC. Jackson
School of Medicine, University of Central Lancashire, Preston, UK
Search for more papers by this authorP. T. Donnan
Dundee Epidemiology and Biostatistics Unit, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorV. H. Santiago
Quality, Safety & Informatics Group, Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, UK
Search for more papers by this authorAbstract
Background
The prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID-exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified.
Methods
A systematic review was performed by identifying studies diagnosing NERD using blinded, placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random-effects meta-analysis.
Results
The prevalence of NERD in adults with asthma was 9.0% (95% CI 6–12%) using OPCTs and 9.9% (95% CI 9.4–10.5%) using self-reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9–97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25–3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15–2.16) and RR 1.59 (95% CI 1.21–2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29–2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12–1.67)) compared to people with NSAID-tolerant asthma.
Conclusions
Respiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self-reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow-up.
References
- 1Zhou Y, Boudreau DM, Freedman AN. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol Drug Saf 2014; 23: 43–50.
- 2Halvorsen S, Andreotti F, ten Berg JM, Cattaneo M, Coccheri S, Marchioli R et al. Aspirin therapy in primary cardiovascular disease prevention: a position paper of the European Society of Cardiology working group on thrombosis. J Am Coll Cardiol 2014; 64: 319–327.
- 3Vandvik PO, Lincoff AM, Gore JM, Gutterman DD, Sonnenberg FA, Alonso-Coello P et al. Primary and secondary prevention of cardiovascular disease: antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(Suppl): e637S–e668S.
- 4Cuzick J, Thorat MA, Bosetti C, Brown PH, Burn J, Cook NR et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol 2015; 26: 47–57.
- 5Mills EJ, Wu P, Alberton M, Kanters S, Lanas A, Lester R. Low-dose aspirin and cancer mortality: a meta-analysis of randomized trials. Am J Med 2012; 125: 560–567.
- 6Gaber F, Daham K, Higashi A, Higashi N, Gulich A, Delin I et al. Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma. Thorax 2008; 63: 1076–1082.
- 7Morales DR, Lipworth BJ, Guthrie B, Jackson C, Donnan PT, Santiago VH. Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: meta-analysis of controlled clinical trials. J Allergy Clin Immunol 2014; 134: 40–45.
- 8Ayres JG, Fleming DM, Whittington RM. Asthma death due to ibuprofen. Lancet 1987; 1: 1082.
- 9Picado C, Castillo JA, Montserrat JM, Agusti-Vidal A. Aspirin-intolerance as a precipitating factor of life-threatening attacks of asthma requiring mechanical ventilation. Eur Respir J 1989; 2: 127–129.
- 10Kwoh CK, Feinstein AR. Rates of sensitivity reactions to aspirin: problems in interpreting the data. Clin Pharmacol Ther 1986; 40: 494–505.
- 11Nizankowska-Mogilnicka E, Bochenek G, Mastalerz L, Swierczynska M, Picado C, Scadding G et al. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy 2007; 62: 1111–1118.
- 12Jenkins C, Costello J, Hodge L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ 2004; 328: 434.
- 13Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
- 14Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.
- 15Ahmetaj NAKF, Lokaj V. Prevalence of Aspirin-Induced Asthma in Certain Group of Kosovo Population and its Presentation. Macedonian J Med Sci 2009; 2: 42–48.
10.3889/MJMS.1857-5773.2009.0028 Google Scholar
- 16Fischer TJ, Guilfoile TD, Kesarwala HH, Winant JG Jr, Kearns GL, Gartside PS et al. Adverse pulmonary responses to aspirin and acetaminophen in chronic childhood asthma. Pediatrics 1983; 71: 313–318.
- 17Rachelefsky GS, Coulson A, Siegel SC, Stiehm ER. Aspirin intolerance in chronic childhood asthma: detected by oral challenge. Pediatrics 1975; 56: 443–448.
- 18Spector SL, Wangaard CH, Farr RS. Aspirin and concomitant idiosyncrasies in adult asthmatic patients. J Allergy Clin Immunol 1979; 64: 500–506.
- 19Tarlo SM, Broder I. Tartrazine and benzoate challenge and dietary avoidance in chronic asthma. Clin Allergy 1982; 12: 303–312.
- 20Towns SJ, Mellis CM. Role of acetyl salicylic acid and sodium metabisulfite in chronic childhood asthma. Pediatrics 1984; 73: 631–637.
- 21Vedanthan PK, Menon MM, Bell TD, Bergin D. Aspirin and tartrazine oral challenge: incidence of adverse response in chronic childhood asthma. J Allergy Clin Immunol 1977; 60: 8–13.
- 22Bavbek S, Yilmaz I, Celik G, Aydin O, Erkekol FO, Orman A et al. Prevalence of aspirin-exacerbated respiratory disease in patients with asthma in Turkey: a cross-sectional survey. Allergol Immunopathol (Madr) 2012; 40: 225–230.
- 23Charpin D, Ramadour M, Lanteaume A, Vervloet D. Triggers in intrinsic asthma in the EGEA study. J Asthma 2003; 40: 87–91.
- 24Eriksson J, Ekerljung L, Bossios A, Bjerg A, Wennergren G, Ronmark E et al. Aspirin-intolerant asthma in the population: prevalence and important determinants. Clin Exp Allergy 2015; 45: 211–219.
- 25Hedman J, Kaprio J, Poussa T, Nieminen MM. Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. Int J Epidemiol 1999; 28: 717–722.
- 26Kasper L, Sladek K, Bochenek G, Duplaga M, Szczeklik A. The frequency of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in the population of adult asthmatics in Poland based on an epidemiological questionnaire. Pneumonol Alergol Pol 2009; 77: 431–439.
- 27Kasper L, Sladek K, Duplaga M, Bochenek G, Liebhart J, Gladysz U et al. Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland. Allergy 2003; 58: 1064–1066.
- 28Mascia K, Haselkorn T, Deniz YM, Miller DP, Bleecker ER, Borish L. Aspirin sensitivity and severity of asthma: evidence for irreversible airway obstruction in patients with severe or difficult-to-treat asthma. J Allergy Clin Immunol 2005; 116: 970–975.
- 29Moon JY, Kim SH, Kim TB, Kim SH, Chang YS, Lee JH et al. Aspirin intolerant asthma in the Korean population: prevalence and characteristics based on a questionnaire survey. Respir Med 2013; 107: 202–208.
- 30Sabry EY. The prevalence of aspirin-induced asthma in Saudian asthmatic patients. Allergol Immunopathol (Madr) 2010; 38: 181–186.
- 31Steppuhn H, Langen U, Scheidt-Nave C, Keil T. Major comorbid conditions in asthma and association with asthma-related hospitalizations and emergency department admissions in adults: results from the German National Health Telephone Interview Survey (GEDA) 2010. BMC Pulm Med 2013; 13: 46.
- 32Vally H, Taylor ML, Thompson PJ. The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients. Thorax 2002; 57: 569–574.
- 33Bavbek S, Dursun AB, Dursun E, Eryilmaz A, Misirligil Z. Safety of meloxicam in aspirin-hypersensitive patients with asthma and/or nasal polyps. A challenge-proven study. Int Arch Allergy Immunol 2007; 142: 64–69.
- 34Berges-Gimeno MP, Simon RA, Stevenson DD. Early effects of aspirin desensitization treatment in asthmatic patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol 2003; 90: 338–341.
- 35Christie PE, Tagari P, Ford-Hutchinson AW, Charlesson S, Chee P, Arm JP et al. Urinary leukotriene E4 concentrations increase after aspirin challenge in aspirin-sensitive asthmatic subjects. Am Rev Respir Dis 1991; 143: 1025–1029.
- 36Falliers CJ. Acetaminophen and aspirin challenges in subgroups of asthmatics. J Asthma 1983; 20: 39–49.
- 37Israel E, Fischer AR, Rosenberg MA, Lilly CM, Callery JC, Shapiro J et al. The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin. Am Rev Respir Dis 1993; 148: 1447–1451.
- 38Kowalski ML, Grzelewska-Rzymowska I, Rozniecki J, Szmidt M. Aspirin tolerance induced in aspirin-sensitive asthmatics. Allergy 1984; 39: 171–178.
- 39Kowalski ML, Grzelewska-Rzymowska I, Szmidt M, Rozniecki J. Bronchial hyperreactivity to histamine in aspirin sensitive asthmatics: relationship to aspirin threshold and effect of aspirin desensitisation. Thorax 1985; 40: 598–602.
- 40Mastalerz L, Sanak M, Kumik J, Gawlewicz-Mroczka A, Celejewska-Wojcik N, Cmiel A et al. Exhaled eicosanoids following bronchial aspirin challenge in asthma patients with and without aspirin hypersensitivity: the pilot study. J Allergy (Cairo) 2012; 2012: 696792.
- 41Micheletto C, Tognella S, Guerriero M, Dal Negro R. Nasal and bronchial tolerability of Rofecoxib in patients with aspirin induced asthma. Eur Ann Allergy Clin Immunol 2006; 38: 10–14.
- 42Nizankowska E, Bestynska-Krypel A, Cmiel A, Szczeklik A. Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma. Eur Respir J 2000; 15: 863–869.
- 43Stevenson DD, Simon RA. Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 2001; 108: 47–51.
- 44Swierczynska M, Nizankowska-Mogilnicka E, Zarychta J, Gielicz A, Szczeklik A. Nasal versus bronchial and nasal response to oral aspirin challenge: clinical and biochemical differences between patients with aspirin-induced asthma/rhinitis. J Allergy Clin Immunol 2003; 112: 995–1001.
- 45Szczeklik A, Nizankowska E, Bochenek G, Nagraba K, Mejza F, Swierczynska M. Safety of a specific COX-2 inhibitor in aspirin-induced asthma. Clin Exp Allergy 2001; 31: 219–225.
- 46Weber EJ, Silverman RA, Callaham ML, Pollack CV, Woodruff PG, Clark S et al. A prospective multicenter study of factors associated with hospital admission among adults with acute asthma. Am J Med 2002; 113: 371–378.
- 47Woessner KM, Simon RA, Stevenson DD. The safety of celecoxib in patients with aspirin-sensitive asthma. Arthritis Rheum 2002; 46: 2201–2206.
- 48Woessner KM, Simon RA, Stevenson DD. Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol 2004; 93: 339–344.
- 49Cormican LJ, Farooque S, Altmann DR, Lee TH. Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity. Clin Exp Allergy 2005; 35: 717–722.
- 50Nizankowska E, Dworski R, Soja J, Szczeklik A. Salicylate pre-treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin-intolerant patients. Clin Exp Allergy 1990; 20: 647–652.
- 51Ameratunga R, Randall N, Dalziel S, Anderson BJ. Samter's triad in childhood: a warning for those prescribing NSAIDs. Paediatr Anaesth 2013; 23: 757–759.
Citing Literature
